↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Träfflista för sökning "WFRF:(Ghosh Fredrik) "

Search: WFRF:(Ghosh Fredrik)

Result 1-50 of 71

Sort/group result

Sort by: Hits per page:

Enumeration	Reference	Cover	Find
1.	Amundadottir, Laufey T., et al. (author) A common variant associated with prostate cancer in European and African populations 2006 In: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658 Journal article (peer-reviewed)abstract With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
2.	Andréasson, Sten, et al. (author) Cone implicit time as a predictor of visual outcome in macular hole surgery. 2014 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 252:12, s. 1903-1909 Journal article (peer-reviewed)abstract To investigate whether preoperative retinal function measured by full-field ERG and multifocal ERG is correlated to postoperative visual acuity after macular hole surgery.
3.	Barth, Henrik, et al. (author) A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute 2016 In: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 254:4, s. 697-703 Journal article (peer-reviewed)abstract Purpose: Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute.Methods: A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry.Results: Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay).Conclusions: Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.
4.	Barth, Henrik, et al. (author) A new model for in vitro testing of vitreous substitute candidates 2014 In: Graefe's Archives for Clinical and Experimental Ophthalmology. - Hedidelberg, Germany : Springer. - 0721-832X .- 1435-702X. ; 252:10, s. 1581-1592 Journal article (peer-reviewed)abstract Purpose: To describe a new model for in vitro assessment of novel vitreous substitute candidates.Methods: The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid (R)), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow (R)). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL.Results: Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid (R)-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow (R)-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow (R) and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid (R)-exposed retinas showed sparse labeling of GFAP.Conclusions: Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid (R) had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow (R) shows protection from culture-induced trauma indicating favorable biocompatibility.
5.	Barth, Henrik, et al. (author) A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades 2021 In: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 46:3, s. 373-379 Journal article (peer-reviewed)abstract PURPOSE: To develop a treatment model of rhegmatogenous retinal detachment (RRD) in which the effects of various vitreous tamponades can be explored.METHODS: In a primary session, detachment was produced in the right eye of 24 rabbits using vitrectomy, posterior vitreous detachment, retinal break induction, and subretinal injection of viscoelastic solution. The following day, detachments were treated in 16 eyes using SF6 (n = 8) or Healaflow® (HF, a cross-linked hyaluronic acid hydrogel, n = 8) tamponade. Animals were followed for 1 month and thereafter examined macroscopically and morphologically in hematoxylin and eosin-stained sections.RESULTS: Retinal detachment (RD) was successfully treated using repeated surgery. Two HF eyes developed progressive vitritis and were excluded from further evaluation. Enlargement of the initial retinal rupture with concomitant RD was seen in 4/8 SF6 eyes, while all 6 HF eyes displayed an attached retina. Attached areas showed a normal retinal morphology except for in 1 HF eye with extensive degeneration.CONCLUSIONS: The RRD repeat vitrectomy model offers a possibility to explore the efficacy and complications of novel potential vitreous tamponades. Gel-based Healaflow® displays excellent anatomic reattachment, however, vitritis and retinal degeneration in some cases warrants further investigation.
6.	Barth, Henrik, et al. (author) Cellular CD68 and CD45r0 positive inflammatory responses of vitrectomy with vitreous substitutes 2016 In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 57:12 Journal article (peer-reviewed)
7.	Barth, Henrik, et al. (author) Developing a retinal detachment model for in vivo testing of vitreous substitutes with repeated pars plana vitrectomy 2018 In: Investigative Ophthalmology and Visual Science. - : Lippincott-Raven Publishers. - 0146-0404 .- 1552-5783. ; 59:9 Journal article (other academic/artistic)
8.	Barth, Henrik, et al. (author) Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model 2019 In: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 257:4, s. 769-783 Journal article (peer-reviewed)abstract PURPOSE: To investigate the inflammatory response of current and future potential vitreous substitutes in an experimental in vivo vitrectomy model.METHODS: Twenty-five gauge pars plana vitrectomy was performed in the right eye of 60 pigmented rabbits, with subsequent injection of 0.5-1.0 ml of Healaflow® (cross-linked hyaluronic acid, n = 12), Bio-Alcamid® (polyalkylimide, n = 8), silicone oil (n = 12), or balanced saline solution (BSS, n = 28). Postoperative clinical evaluation was performed; and the rabbits were sacrificed at 1 day, 1 week, or 1 month. The eyecups were then examined macroscopically; the retinas sectioned and stained with hematoxylin and eosin (Htx), and immunohistochemically labeled for glial fibrillary acidic protein (GFAP), CD45, galectin-3, CD68, and CD20. Unoperated left eyes from treated animals as well as eyes from untreated animals were used as controls.RESULTS: Vitrectomy without major complications was achieved in 46/60 eyes. The remaining 14 eyes were analyzed separately. One eye developed endophthalmitis after 1 week and was excluded. Eyes treated with Healaflow®, silicone oil, and BSS had a comparable appearance macroscopically and in Htx-stained sections, whereas Bio-Alcamid®-injected eyes exhibited increased macroscopic inflammation and severely affected retinas. GFAP upregulation was present in all treatment groups, most prominent in eyes treated with Bio-Alcamid® and silicone oil. Upregulation of CD45 and CD68 in the inner retina and vitreous space was most prominent with Bio-Alcamid® treatment, and these eyes together with their silicone oil-treated counterparts also displayed a stronger upregulation of CD20-labeled cells compared with remaining groups. General upregulation of galectin-3, mainly in the inner retina, was found in all groups. In eyes with perioperative complications, labeling of CD45, CD68, and especially GFAP was comparably high.CONCLUSIONS: We here describe differences in the postsurgery inflammatory profiles of existing and potential vitreous substitutes. Bio-Alcamid® and silicone oil display severe signs of gliosis and inflammation, whereas Healaflow® elicits minimal reactions comparable with BSS, highlighting its potential application as a vitreous substitute in a future clinical setting.
9.	Berntsson, Fredrik, et al. (author) A one dimensional model of blood flow through a curvilinear artery 2018 In: Applied Mathematical Modelling. - : ELSEVIER SCIENCE INC. - 0307-904X .- 1872-8480. ; 63, s. 633-643 Journal article (peer-reviewed)abstract We present a one-dimensional model describing the blood flow through a moderately curved and elastic blood vessel. We use an existing two dimensional model of the vessel wall along with Navier-Stokes equations to model the flow through the channel while taking factors, namely, surrounding muscle tissue and presence of external forces other than gravity into account. Our model is obtained via a dimension reduction procedure based on the assumption of thinness of the vessel relative to its length. Results of numerical simulations are presented to highlight the influence of different factors on the blood flow. (C) 2018 Elsevier Inc. All rights reserved.
10.	Bro, T, et al. (author) Floorball-related eye injuries: The impact of protective eyewear. 2016 In: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 1600-0838 .- 0905-7188. Journal article (peer-reviewed)abstract Several previous studies have shown that floorball belongs to a high-risk group of sports in terms of eye injuries. Protective eyewear is available, but the extent of its use and impact on eye injuries are unknown. The purpose of this study was to investigate the current incidence of eye injuries caused by floorball and to compare it with the present use of protective eyewear. Medical records were used to identify all eye injuries suffered while playing floorball in Jönköping County from 2008 to 2011 (N = 167). All these patients were sent a questionnaire that included inquiries about the use of protective eyewear. The study shows that floorball caused more eye injuries than all other sports combined (56%). Prolonged decreased visual acuity was very unusual (0.5%), but moderate eye injuries with some risk of future problems were seen in 62% of the sample. More than one fifth of the injured patients reported some kind of vision-related problem 2-7 years after the original injury. Only one player had been using protective eyewear at the time of injury. Our results underline the importance of protective eyewear to prevent floorball-related injuries.
11.	Cardiakidis Myers, Anna, et al. (author) Intravitreal Injection of Triamcinolone Acetonide into Healthy Rabbit Eyes Alters Retinal Function and Morphology 2013 In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:6, s. 649-661 Journal article (peer-reviewed)abstract Aim: To study the effects of intravitreally injected triamcinolone acetonide (TA) and/or its preservative benzyl alcohol (BA) in healthy rabbit retina. Methods: Forty-eight rabbits (aged 4 months, body weight approximate to 3 kg) were randomized into four groups (n=12). They were examined with electroretinography (ERG) prior to drug exposure, and then injected intravitreally with a combination of TA and BA, TA without BA, BA alone or a balanced saline solution (BSS). The electroretinograms were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and the sectioned retinas were studied. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Muller cells. Results: Rabbits injected with BA showed a significantly lower rod-mediated b-wave amplitude than the controls 1 week after injection. TA-injected rabbits demonstrated significantly higher a- and b-wave amplitudes in the total retinal response than the controls 1 week post-injection. The rabbits injected with TA+BA demonstrated a significantly higher b-wave amplitude in the total retinal response than the controls 1 week after injection. The significantly higher a-wave amplitude in the total retinal response remained in the TA-injected rabbits 7 weeks after injection. Immunohistochemistry revealed that protein kinase C alpha (PKC alpha) was down-regulated in both the perikarya and the axons of bipolar cells in histological sections from rabbit retina injected with TA+BA, BA and TA. Conclusions: Intravitreal injection of the preservative BA reduces the isolated rod-mediated retinal response in the rabbit, transiently and selectively. Intravitreal injection of TA increases the total retinal response in the rabbit up to seven weeks after injection. The effects observed are not only limited to retinal function, but also include changes in the expression of PKC alpha in rod bipolar cells, indicating drug-related interference with normal retinal physiology in the healthy rabbit eye.
12.	Cardiakidis Myers, Anna, et al. (author) Retinal function and morphology in rabbit after intravitreal injection of VEGF inhibitors. 2012 In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:5, s. 399-407 Journal article (peer-reviewed)abstract Purpose/Aim: To explore changes in morphology and function in the rabbit retina after intravitreal high-dose injection of three commonly used VEGF inhibitors. Materials and methods: Forty-eight rabbits of mixed strain (6 months of age, body weight ≈ 3 kg) were randomized into four groups (n = 12). They were examined with full-field electroretinography (ERG) and with multifocal electroretinography (mf ERG) prior to drug exposure. The rabbits were then injected intravitreally with bevacizumab, ranibizumab, pegaptanib, or with a balanced saline solution. The dose of VEGF inhibitor was chosen to achieve a vitreous concentration approximately three times higher than the one clinically used in the adult human eye. ERG was then performed 8 weeks postinjection, and mf ERG 9 weeks postinjection. After 9 weeks, the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemical analysis was performed of rods, cones, rod bipolar cells, horizontal cells, and amacrine cells. Results: Rabbits injected with VEGF inhibitors all showed significantly lower amplitude of the dark-adapted b-wave rod-mediated response to dim light, compared to the rabbits injected with BSS. The a wave (reflecting photoreceptor function) in the response to single flash white light was however not affected. Immunohistochemistry revealed a significant reduction in PKC labeling of rod bipolar cells in pegaptanib and ranibizumab injected eyes whereas bevacizumab injected eyes displayed normal PKC labeling. No apparent morphological change was seen with markers for remaining retinal cells. Conclusions: Our results indicate that the use of high-dose intravitreal VEGF inhibitors in the rabbit eye affects rod-mediated retinal function and PKC expression in rod bipolars cells for at least 9 weeks after drug administration. The three VEGF inhibitors influence the retina slightly differently. These results are important for the understanding of drug action and when devising therapeutical strategies in new areas such as retinopathy of prematurity where vitreous volume is significantly lower compared to the adult eye.
13.	Cardiakidis Myers, Anna, et al. (author) Retinal Function and Morphology in the Rabbit Eye after Intravitreal Injection of the TNF Alpha Inhibitor Adalimumab. 2014 In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 39:11, s. 1106-1116 Journal article (peer-reviewed)abstract Abstract Aim: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. Methods: Forty-eight rabbits of mixed strain (9-12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin-eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. Results: No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. Conclusions: Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina.
14.	Cardiakidis Myers, Anna, et al. (author) Rifabutin accumulates in the lens and reduces retinal function in the rabbit eye 2009 In: Retina. - 0275-004X. ; 29:1, s. 106-111 Journal article (peer-reviewed)abstract PURPOSE: To study the toxicology of rifabutin in the rabbit eye with emphasis on retinal function and histopathology.METHODS: Seven rabbits received a daily dose of rifabutin during 15 months. Six rabbits receiving only the vehicle were used as controls. Repeated standardized full-field electroretinograms (ERG) were assessed. After discontinuing treatment, the rabbits were killed and the cornea, the lens, and the sectioned retina was studied. Immunhistochemistry directed against vimentin, glial fibrillaryacidic protein (GFAP), protein kinase C (PKC), and peanut agglutinin (PNA) was performed.RESULTS: Rifabutin was detected in serum of the treated rabbits. During treatment, the full-field ERG demonstrated significantly reduced b-wave amplitudes in the total rod-cone response as well as in the isolated rod and cone response compared with the recordings before treatment. The control rabbits did not demonstrate a reduction of the ERG amplitudes. The treated rabbits developed a discoloration of the lens, not seen in the control group. No retinal pathology was demonstrated using immunohistochemical methods.CONCLUSION: Rifabutin causes a discoloration of the lens and reduces both rod and cone function in rabbits, but does not alter retinal morphology. Previous reports on ocular side effects caused by rifabutin are supported by the results of this study.
15.	Cederlund, Martin, et al. (author) Vitreous levels of oxidative stress biomarkers and the radical-scavenger α(1)-microglobulin/A1M in human rhegmatogenous retinal detachment. 2013 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 251:3, s. 725-732 Journal article (peer-reviewed)abstract PURPOSE: To explore oxidative stress and the radical scavenger α(1)-microglobulin (A1M) in the vitreous body of human eyes with primary rhegmatogenous retinal detachment (RRD). METHODS: Levels of carbonyl groups, a marker of oxidative stress, and A1M were measured by ELISA and RIA in 14 vitreous samples derived from patients suffering from RRD, and compared with 14 samples from macula hole (MH) patients. Carbonyl group and A1M levels in RRD samples were statistically related to detachment characteristics. Analysis of total protein level, SDS-PAGE, and Western blotting of A1M was also performed. In a separate experiment, mRNA expression of A1M was measured by RT-PCR in rat retina explants. RESULTS: Levels of carbonyl groups and A1M varied widely in RRD vitreous samples, but were significantly higher in samples derived from eyes with large detachment area and macula-off status, while the presence of vitreous hemorrhage did not show any significant correlation. Compared with MH samples, RRD samples displayed significantly higher levels of A1M, whereas changes in total protein levels and carbonyl groups were not significant. Novel forms of A1M, not previously seen in plasma, were found in the vitreous body by Western blotting. Furthermore, A1M expression was seen in rat retina explants and was upregulated after 24 h of culturing. CONCLUSION: Oxidative stress is a prominent feature of human eyes with primary RRD, and is directly related to detachment severity. Affected eyes can launch a protective response in the form of the radical scavenger A1M possibly derived from the retina. The results thus indicate potential therapeutic cell loss prevention in RRD by employing the endogeneous radical scavenger A1M.
16.	Crafoord, Sven, et al. (author) Experimental vitreous tamponade using polyalkylimide hydrogel 2011 In: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 249:8, s. 1167-74 Journal article (peer-reviewed)abstract PURPOSE: To evaluate polyalkylimide as a possible vitreous tamponading agent.METHODS: A 20-gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkylimide (Bio-Alcamid) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy.RESULTS: The viscoelastic hydrogel was successfully injected, and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod- and cone-derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus, while the peripheral part appeared intact.CONCLUSION: Polyalkylimide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.
17.	Crafoord, Sven, 1950-, et al. (author) Vitreous biochemistry and artificial vitreous 2014. - 1 In: Vitreous. - New York, USA : Springer. - 9781493910854 - 9781493910861 ; , s. 81-92 Book chapter (other academic/artistic)
18.	Engelsberg, Karl, et al. (author) Development of the Embryonic Porcine Neuroretina in vitro. 2005 In: Ophthalmic Research. - : S. Karger AG. - 1423-0259 .- 0030-3747. ; 37:2, s. 104-111 Journal article (peer-reviewed)abstract <i>Purpose:</i> The objective of this study was to investigate the survival and morphology of embryonic porcine full-thickness neuroretina in culture. <i>Methods:</i> Porcine fetuses were taken out by cesarian section, and the eyes were enucleated. Neuroretinas were explanted on culture plate inserts and were kept for 0–42 days in vitro under standard culture conditions. Green nucleic acid (Sytox) was used for measuring the extent of cell death, and 4,6-diaminidine-2-phenylindoldihydrochloride was used as a marker for the cellular layers. The explants were examined as whole-mount preparations and vertical sections. Sectioned tissue was stained with hematoxylin-eosin and labeled for immunohistochemistry with photoreceptor-specific antibodies raised against transducin and recoverin. <i>Results:</i> In explants kept for 0–5 days in vitro, the developing retina consisted of multiple rows of neuroblastic cells and a more defined, but multilayered ganglion cell layer (GCL). Older explants revealed a more differentiated appearance with ultimately all normal retinal layers present, even after 42 days in vitro. Transducin- and recoverin-labeled photoreceptors were seen in these specimens, but no outer segments were found. The whole-mount preparation revealed extensively Sytox-labeled cells in the GCL at 2 days in vitro, but very few cells were labeled in older explants. <i>Conclusion:</i> This study shows that cultured fetal porcine full-thickness neuroretina can survive and develop according to its intrinsic timetable for at least 6 weeks in vitro. The in vitro system for culturing of the full-thickness retina may be useful in experiments involving retinal transplantation.
19.	Engelsberg, Karl, et al. (author) Early development of retinal subtypes in long-term cultures of human embryonic retina. 2008 In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 33:2, s. 185-191 Journal article (peer-reviewed)abstract Purpose: To study early signs of neuronal and glial differentiation in the human embryonic retina. Materials and Methods: 6.5-to 8-week-old human embryos were obtained from elective abortions. The neuroretinas were kept in culture as full-thickness sheets for 7-42 days. Results: The control retinas consisted of a neuroblast cell layer and a thin marginal zone. Most explants displayed presence of retinal lamination, but also contained regions of disorganization. Vimentin labeling showed vertically arranged Müller cells in all explants. Recoverin-labeled photoreceptors appeared in explants kept 14 days and longer. By labeling with antibodies against PKC and parvalbumin, rod bipolar cells and amacrine cells could be seen in explants kept for 42 days in culture.Conclusions: We have shown that the embryonic full-thickness neuroretina can survive in a culture environment for at least 6 weeks, and can develop several types of the retina-specific neuronal and glial cells.
20.	Engelsberg, Karl, et al. (author) Human Retinal Development in an in situ Whole Eye Culture System. 2011 In: Developmental Neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 33, s. 110-117 Journal article (peer-reviewed)abstract Phenotypic characterization of human retinogenesis may be facilitated by use of the tissue culture system paradigm. Traditionally, most culture protocols involve isolation of retinal tissue and/or cells, imposing various degrees of trauma, which in many cases leads to abnormal development. In this paper, we present a novel culture technique using whole embryonic eyes to investigate whether the retina in situ can develop normally in vitro. All procedures were carried out in accordance with the Declaration of Helsinki. Human embryos were obtained from elective abortions with the informed consent of the women seeking abortion. A total of 19 eyes were enucleated. The ages of the embryonic retinas were 6-7.5 weeks. Eyecups from 2 eyes were fixed immediately, to be used as controls. The remaining 17 eyes were placed on culture plates and divided into 3 groups kept for 7 (n = 4), 14 (n = 7) and 28 (n = 6) days in vitro (DIV). After fixation, the specimens were processed for hematoxylin and eosin staining, immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Antibodies against recoverin (rods and cones), protein kinase C (PKC; rod bipolar cells) and vimentin (Müller cells) were used. TUNEL was used to detect apoptotic cells. In hematoxylin- and eosin-stained sections, the control retinas displayed a neuroblast cell layer (NBL) and an inner marginal zone. Specimens kept 7-14 DIV had a similar appearance, while 28-day specimens consisted of an NBL with almost no marginal zone. Thirteen of the 17 cultured retinas displayed completely normal lamination without rosettes or double folds. Pyknotic cells were found at the inner margin of the retinas, and the proportion of these cells increased with time in vitro. TUNEL staining revealed a few scattered cells in 7-DIV specimens, and the amount of stained cells in the inner part of the retinas progressively increased in 14- and 28-DIV specimens. Vimentin labeling showed cells arranged in a vertical pattern in all retinas. Labeling with recoverin revealed photoreceptors in 4 of the retinas kept for 14 DIV, and in all retinas kept for 28 DIV. After 28 DIV, 2 of the eyes labeled with PKC contained rod bipolar cells with minimal axons. Here we showed that human embryonic retinas can be kept in culture in situ within the eye for at least 4 weeks. Abnormal lamination is not as frequent as in isolated full-thickness retinas, indicating that physical and biochemical contact with surrounding tissues is vital for proper development. Several types of the retina-specific neuronal and glial cells were seen to differentiate according to the in vivo schedule. The results are important for future studies of retinal development, and the technique can also be used for testing the effects of various drugs on the immature retina.
21.	Engelsberg, Karl, et al. (author) Transplantation of cultured adult porcine full-thickness retina. 2007 In: Cell Transplantation. - 1555-3892. ; 16:1, s. 31-39 Journal article (peer-reviewed)abstract In this study we wanted to examine how an adult neuroretina from an animal with an eye similar to the human one survives in vitro. We also wanted to investigate how the culture process affects the adult retina when used in a transplantation paradigm. Full-thickness neuroretinal sheets from adult porcine eyes were dissected into pieces measuring 3 mm in diameter. These were kept in culture for 1-3 days. After this time, the explants were fixed or transplanted subretinally to adult pigs, which were killed after 72-74 days. Transplanted eyes, as well as tissue kept in culture only, were processed for hematoxylin and eosin staining and immunohistochemistry. Explants kept I day in vitro (DIV) displayed the normal morphology. In these specimens, single pyknotic cells were evident in the outer nuclear layer (ONL) and ganglion cell layer, but were more frequent in the inner nuclear layer (INL). After longer times in vitro, severe degenerative changes appeared. Transplanted explants kept I DIV prior to transplantation exhibited normal retina] lamination in two out of four specimens. Transducin and recoverin labeling revealed photoreceptors with inner segments in these grafts. Rod bipolar cells displayed a normal morphology. Vertically arranged Muller cells were also seen in the laminated grafts. Two of the three transplants kept 2 DIV displayed minimal lamination. Eyes with transplants kept 3 DIV prior to transplantation displayed degenerated grafts in all eyes. This study shows that adult porcine neuroretinal explants kept in culture for I day display a normal morphology in their major part. Additionally, 1-day explants can survive transplantation with retained morphology even after several months. This indicates the possibility of storing adult donor tissue between harvest and transplantation. The culture system may also be used in the future as a tool for manipulating retina] donor tissue prior to transplantation.
22.	Engelsberg, Karl, et al. (author) Uremic Optic Neuropathy with Severe Epiretinal Membrane Formation 2012 In: Retinal Cases & Brief Reports. - 1935-1089. ; 6:2, s. 5-172 Journal article (peer-reviewed)
23.	Gesslein, Bodil, et al. (author) Protein kinase C in porcine retinal arteries and neuroretina following retinal ischemia-reperfusion. 2009 In: Molecular Vision. - 1090-0535. ; 15:Apr 13, s. 737-746 Journal article (peer-reviewed)abstract PURPOSE: Identification of the intracellular signal-transduction pathways activated in retinal ischemia may be important in revealing novel pharmacological targets. To date, most studies have focused on identifying neuroprotective agents. The retinal blood vessels are key organs in circulatory failure, and this study was therefore designed to examine the retinal vasculature separately from the neuroretina. METHODS: Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes, followed by 5, 12, or 20 h of reperfusion. Protein kinase C (PKC)alpha, PKCbeta1, and PKCbeta2 mRNA levels, and protein expression were determined using real-time PCR, western blot, and immunofluorescence staining techniques. RESULTS: The retinal arteries could easily be dissected free and studied separately from the neuroretina in this porcine model. The PKCalpha, PKCbeta1, and PKCbeta2 mRNA levels tended to be lower in ischemia-reperfused than in sham-operated eyes in both the retinal arteries and the neuroretina. This was most prominent after 5 h, and less pronounced after 12 h and 20 h of reperfusion. Likewise, the protein levels of PKCalpha, PKCbeta1, and PKCbeta2 were slightly lower following ischemia-reperfusion when compared to sham-operated eyes. PKCalpha, PKCbeta1, and PKCbeta2 immunostaining were observed in bipolar cells of the neuroretina and in endothelial cells, and to a low extent in the smooth muscle layer, of the retinal arteries. CONCLUSIONS: Retinal ischemia followed by reperfusion results in lower levels of PKC in both the neuroretina and retinal arteries. New targets for pharmacological treatment may be found by studying the retinal vasculature so as to identify the intracellular signal-transduction pathways involved in the development of injury following retinal circulatory failure.
24.	Ghosh, Fredrik, et al. (author) Acute tissue reactions, inner segment pathology, and effects of the antioxidant α1-microglobulin in an in vitro model of retinal detachment 2018 In: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 173, s. 13-23 Journal article (peer-reviewed)abstract The purpose of this study was to explore acute tissue reactions, ultrastructural photoreceptor morphology with emphasis on inner segments, and the effect of antioxidant treatment in an in vitro model of rhegmatogenous retinal detachment (RRD). A previously described method of RRD simulation was used with adult retinal porcine explants kept free-floating in culture medium with or without treatment with the radical scavenger α1-microglobulin (A1M). Explants were examined at 5 time points from 1 to 24 h using transmission electron microscopy as well as quantitative real-time PCR (RT-PCR) to quantify gene expression of the cell stress marker heat shock protein 70 (Hsp70) and oxidative stress marker heme oxygenase (HO-1). The culture medium level of the cell damage marker lactate dehydrogenase (LDH) and oxidative stress DNA damage marker 8-Oxo-2'-deoxyguanosine (8-OHdG) was also assessed at each time point. We found that the levels of Hsp70 and LDH rapidly increased in both groups, and at 3 and 6 h, Hsp70 was significantly higher in A1M treated retinas. At 24 h, Hsp70 and LDH, as well as 8-OHdG were significantly lower compared with controls, whereas the tissue level of HO-1 was significantly higher. Progressive ultrastructural photoreceptor changes were seen in untreated control explants from 1 h and onwards including outer segment shortening and loss, disruption of organelles within the inner segments and loss of perikarya in the outer nuclear layer. Inner segment pathology was more rapid and extensive in rods compared with in cones. In A1M treated counterparts, damage to rod inner segment mitochondria was significantly higher after 1 h of culture, but after this time, no statistical difference was found. At 24 h, cone inner segment mitochondrial disruption was significantly higher in control retinas and the number of surviving perikarya lower. From our results, we conclude that retinal explants elicit acute cell stress reactions when placed in culture without physical support simulating a detached retina floating in the vitreous space. Photoreceptors rapidly display degenerative changes including extensive damage to inner segment mitochondria indicating loss of energy transduction as an early key event. A1M increases initial mitochondrial stress in the rods, however, subsequent pathology is attenuated by the treatment, highlighting the dynamics of protective as well as disruptive oxidative stress reactions in the detached retina.
25.	Ghosh, Fredrik, et al. (author) Cell Type Differentiation Dynamics in the Developing Porcine Retina. 2010 In: Developmental Neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 32, s. 47-58 Journal article (peer-reviewed)abstract The dynamics of retinal embryogenesis have been well characterized previously in terms of cell proliferation, genesis and migration, whereas overall cell type differentiation within the retinal layers has been less thoroughly explored. In the present study, phenotypical differentiation of all 7 major retinal cell types was examined in the developing porcine retina using one cell-specific immunohistochemical marker per cell type. At the end of the first trimester at E39 (39 days after gestation), neurofilament labeled ganglion cells, recoverin labeled photoreceptors, vimentin labeled Müller cells and synaptophysin labeled presynaptic vesicles were found. Rhodopsin labeled rod photoreceptors were present at E60, whereas cone transducin labeled cone photoreceptors were not seen until E99. Differentiation of inner nuclear cells coincided with the appearance of the retinal layers at E70-E99 with the presence of parvalbumin labeled amacrine cells, calbindin labeled horizontal cells and PKC labeled rod bipolar cells. At postnatal day 4, all retinal subtypes except for cone photoreceptors displayed a labeling pattern corresponding to the one found in the adult porcine retina. The immunohistochemical labeling pattern suggests that phenotypic differentiation of the 7 principal retinal cell types in the porcine retina follows a central-to-peripheral spatio-temporal gradient similar to the one reported for cell proliferation and genesis. Differentiation of the non-laminated retinal cell mass appears to be initiated at its outer and inner margins and progresses inwards, a process which ends in the formation of the characteristic plexiform and nuclear layers. The dynamics of retinal cell type differentiation are of interest from a biological standpoint and are also important for therapeutical strategies in retinal degenerative disease.
26.	Ghosh, Fredrik, et al. (author) Exogenous Glutamate Modulates Porcine Retinal Development in vitro. 2012 In: Developmental Neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. Journal article (peer-reviewed)abstract Embryogenesis of the retina is a complex event orchestrated by a multitude of physical and biochemical signals. To study the impact of intrinsic developmental cues, the retinal tissue can be isolated in culture which also enables modulation of normal development for other purposes, i.e. transplantation of specific neuronal cell types. In the present experiment, cell type development of immature porcine retinal tissue kept in culture was explored using specific immunohistochemical markers. Retinal explants were either kept under standard culture conditions or supplemented with glutamate and their morphology was compared with in vivo controls of corresponding age. After 15 days in vitro (DIV), E45 retinal explants displayed several signs of atypical development when compared with E60 in vivo controls. First, an accelerated photoreceptor differentiation was evident, seen in sections labeled with antibodies directed against recoverin, rhodopsin and synaptophysin. Second, apoptotic cells in the inner retina were more prevalent in the cultured retinas (TUNEL). Rod photoreceptor differentiation as well as inner retinal apoptosis was even more pronounced in glutamate-supplemented specimens in which they occurred already at 8 DIV. Müller cell, vimentin and GFAP expression was not affected in any of the cultured retinas. These results suggest that normal retinal embryogenesis is more dependent on tissue extrinsic factors than what has been deduced from previous small animal experiments. Glutamate, which has been identified as an important regulator of cell cycle exit, may also be important for photoreceptor differentiation and induction of developmental apoptosis. Insights into retinal cell type differentiation under in vitro conditions is of interest from a biological standpoint, and the possibility of modulation of this process is valuable for research directed towards cell replacement in retinal degenerative disease.
27.	Ghosh, Fredrik (author) Experimental Neuroretinal Transplantation 1999 Doctoral thesis (other academic/artistic)abstract Embryonic full-thickness rabbit neuroretinal sheets were transplanted to the subretinal space of adult hosts. This was accomplished by using a new transplantation technique involving vitrectomy and retinotomy. The grafts were followed from 10 to 306 days after surgery, and were then examined by different histological techniques. In the light microscope, the transplants were seen to develop the normal retinal lamination and fused with the host retina, especially after long survival times. Ultrastructurally, normal photoreceptor outer segments, well integrated with the host retinal pigment epithelium were found. Growth cones were present in the zone of fusion between graft and host retina. Immunohistochemical labeling revealed many of the normal retinal components not previously found in retinal transplants, and graft-host connections between neurons in the rod pathway were seen. The morphology of vibratome sectioned neuroretinal sheets as well as adult full-thickness grafts was also examined. These transplantation types showed less of the normal morphology compared with embryonic full-thickness grafts. The immunogenicity of embryonic full-thickness and fragmented grafts was compared using Major Histocompatibility Complex (MHC) immunolabeling. Fragmented grafts elicited a response from the host immune system similar to a chronic transplant rejection. This reaction was absent in the full-thickness grafts which is in accordance with their good long-term survival.
28.	Ghosh, Fredrik, et al. (author) Immune privilege of allogeneic neuroretinal transplants in the subconjunctival space. 2008 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 246, s. 1715-1722 Journal article (peer-reviewed)abstract BACKGROUND: The extent of site and tissue-associated immune privilege is of great interest in transplantation experiments involving the CNS. In the present paper we have explored neuroretinal immune privilege by transplantation to a non-immune privileged site. METHODS: Fetal and adult full-thickness rabbit neuroretinal grafts were placed in the subconjunctival space of immunocompetent rabbit hosts. Morphological examination was performed after 2-31 days (fetal grafts, n = 46), and after 8 days (adult grafts, n = 4). RESULTS: Hematoxylin and eosin-stained sections and immunohistochemistry directed against microtubule-associated protein 2 (MAP2) revealed surviving grafts containing retinal neurons in the majority of eyes with fetal grafts. In all specimens, a mild inflammatory reaction was evident as seen with major histocompatibility complex class II (MHC-II) labeling. Short-term grafts survived well and displayed lamination and rosette formation whereas older grafts appeared more disorganized and were more often rejected. Müller cell fibers labeled with glial fibrillary acidic protein (GFAP) were present in grafts from 15 days and onwards. Adult grafts were destroyed after 8 days. CONCLUSIONS: Allogeneic fetal full-thickness neuroretinal transplants can survive for several weeks in a non-immune privileged environment in which adult grafts are rapidly rejected. Fetal grafts gradually shrink, lose their architecture and go through a glial transformation accompanied by low-grade inflammation. The rabbit neuroretina thus appears to enjoy partial immune privilege, the extent of which depends on the development state of the tissue. The characterization of neuroretinal immune privilege will hopefully influence future clinical trials of retinal transplantation.
29.	Ghosh, Fredrik, et al. (author) In vitro biomechanical modulation-retinal detachment in a box. 2016 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 254:3, s. 475-487 Journal article (peer-reviewed)abstract To illustrate the importance of biomechanical impact on tissue health within the central nervous system (CNS), we herein describe an in vitro model of rhegmatogenous retinal detachment (RRD) in which disruption and restoration of physical tissue support can be studied in isolation.
30.	Ghosh, Fredrik, et al. (author) Intravitreal sustained-release ganciclovir implants for severe bilateral cytomegalovirus retinitis after stem cell transplantation. 2002 In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 80:1, s. 101-104 Journal article (peer-reviewed)abstract Purpose: To describe the treatment of cytomegalovirus (CMV) retinitis with intravitreal sustain-release ganciclovir devices in a 16-year-old patient in third remission of acute lymphoblastic leukemia after stem cell transplantation. METHODS: The patient received a stem cell transplant from an unrelated bone marrow donor after which he contracted a serious CMV infection manifested in the lungs and retinae. His immune system at this time was almost completely depleted. Implantation of a sustained-release ganciclovir device was performed in both eyes when retinitis progressed in spite of aggressive antiviral intravenous treatment. RESULTS: No per- or postoperative complications were noted. Infiltrates, hemorrhages and macular edema present preoperatively dissolved over a period of six months. The final visual acuity was 1.0 in both eyes. The patients immune system and lung function slowly recovered during the same time period. CONCLUSIONS: The intravitreal ganciclovir implant provides safe and effective therapy against CMV retinitis, and should be considered in patients acquiring the infection after stem cell transplantation.
31.	Ghosh, Fredrik, et al. (author) Isolation of photoreceptors in the cultured full-thickness fetal rat retina. 2009 In: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 50, s. 826-835 Journal article (peer-reviewed)abstract Purpose. To create a retina consisting mainly of photoreceptors for future use as donor tissue in retinal transplantation. Methods. Fetal full-thickness neuroretinas from Sprague Dawley rats 17 (E17) or 20 (E20) days post conception were placed in culture for 7 or 14 days. Explants and age-matched control retinas were examined by light microscopy and with a panel of immunohistochemical markers labeling all seven of the major retinal cell types. Results. E17 and E20 control retinas displayed vimentin labeled Muller cells, NF160 labeled ganglion cells and synaptic vesicles labeled with synaptophysin. The remaining cell types were found in control specimens of postnatal age 2 days and older. After 7 or 14 days in culture, all explants were significantly thinner than their aged-matched controls, and displayed multiple rows of cells organized in a single layer. Within this layer, they contained rhodopsin labeled rod photoreceptors, presynaptic vesicles and vertically arranged Muller cells. Transducin labeled cone photoreceptors were found in all but the youngest explants. Scattered PKC labeled rod bipolar cells and calbindin labeled horizontal cells were found in the inner part of most explants whereas beta-III-tubulin labeled ganglion cells and parvalbumin labeled amacrine cells were seen only sporadically. No NF160 labeled ganglion cells were found. Conclusions. Fetal full-thickness rat retina in vitro develops into a retina consisting of predominantly synapse containing cone and rod photoreceptors embedded in a scaffold of well organized Muller cells. These explant retina characteristics are well adapted for use as donor tissue in future retinal transplantation experiments.
32.	Ghosh, Fredrik, et al. (author) Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa. 2007 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 245:6, s. 835-846 Journal article (peer-reviewed)abstract The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Muller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.
33.	Ghosh, Fredrik, et al. (author) Müller cells in allogeneic adult rabbit retinal transplants. 2002 In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 40:1, s. 78-84 Journal article (peer-reviewed)abstract Müller cell morphology and degree of activation in adult retinal transplants have, to our knowledge, never been reported previously. We transplanted adult rabbit neuroretinal full-thickness sheets, prepared under strict control, to the subretinal space of adult rabbits. After surviving 6-174 days, eyes were examined in the light microscope, and grafts displaying the normal laminated morphology were labeled with antibodies against vimentin and glial fibrillary acidic protein (GFAP). Müller cells in the grafts displayed the normal vertical arrangement, from outer limiting membrane to vitread endfeet. They showed an initial degree of activation, evident by GFAP upregulation, which diminished with increasing survival times, and was absent in the oldest specimens. In the host retina, Müller cells in the transplant area became progressively more disorganized with increasing survival times, and their degree of activation increased. Our results suggests that adult full-thickness neuroretinal grafts are structurally stable, even in long-term specimens, and thrive in spite of their allogeneic environment. The gliotic change seen in the host retina covering the graft is identical to the one seen in earlier reported eyes receiving embryonic grafts, and is due to the merangiotic nature of the rabbit neuroretina. GLIA 40:78-84, 2002. Copyright 2002 Wiley-Liss, Inc.
34.	Ghosh, Fredrik (author) Müller cells in long-term full-thickness retinal transplants. 2002 In: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 37:1, s. 76-82 Journal article (peer-reviewed)abstract Müller cells are essential in creating and maintaining intricate neuroretinal architecture. The functions of this important glial cell are not limited to mere support of the retinal neurons, but also include interaction in synaptic transmission and activation in response to retinal insult. In this study, we have examined Müller cell morphology and degree of activation in embryonic full-thickness rabbit neuroretinal grafts, which were positioned under the host retina using vitrectomy technique. After surviving 3-10 months, retinal specimens were examined with hematoxylin and eosin staining and immunohistochemical analysis of vimentin and glial fibrillary acidic protein (GFAP) expression. In the host retina covering the graft, outer layers were degenerated, and vimentin-labeled Müller cells in this area appeared short, disorganized, and displayed strong GFAP labeling. In the graft, vimentin-labeled Müller cells spanning the retinal layers in the normal manner were found. Müller cells in 3-month grafts were well labeled by GFAP, whereas in older grafts, GFAP labeling was very weak or absent. Our results suggest that Müller cells in well-laminated full-thickness retinal grafts display many of the normal morphological features and retain a normal organization even after prolonged survival times. The loss of the initial degree of Müller cell activation indicates a long-term stability of the graft. The degeneration and gliosis of the host retina covering the graft is best explained by the merangiotic nature of the rabbit retina and may limit the usefulness of the rabbit in retinal transplantation experiments.
35.	Ghosh, Fredrik, et al. (author) Neuronal and Glial Alterations in Complex Long-Term Rhegmatogenous Retinal Detachment. 2012 In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:8, s. 704-711 Journal article (peer-reviewed)abstract Purpose: To explore neuronal and glial alterations in eyes with complex long-term rhegmatogenous retinal detachment (RRD). Methods: Morphological analysis was performed on eight retinal specimens derived from patients treated with peripheral retinectomy for RRD complicated by retinal shortening or retinal thinning. All eyes had undergone previous surgeries including silicone oil tamponade, and had a median total detachment time of 2.5 months (range 2-12). Specimens were examined with hematoxylin and eosin staining and immunohistochemistry directed against activated Müller cells, ganglion cells, rod bipolar cells, and photoreceptors. Results: Retinal specimens displayed severe loss of photoreceptor and rod bipolar cells. Remaining neuronal cells exhibited disorganized perikarya and neurites with disruption of the normal retinal lamination. Müller cell activation was evident in all specimens with subretinal and epiretinal hypertrophy present in tissue derived from shortened retinal detachments. Conclusion: Long-term RRD leads to retinal remodeling characterized by loss of first and second order retinal neurons, disruption of the entire retinal lamination and gliosis. The severity of histopathological changes indicates that anatomical as well as functional recovery of the involved retina is precarious. The findings may be important when devising surgical strategies to avoid permanent retinal detachment.
36.	Ghosh, Fredrik, et al. (author) Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination. 2008 In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 152:Jan 4, s. 526-533 Journal article (peer-reviewed)abstract In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival. Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dawley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days. Surviving full thickness grafts were found in six of eight eyes, four of which displayed the normal laminated appearance. Major histocompatibility complex (MHC) up-regulation in surviving grafts was minimal and they contained a well-organized photoreceptor layer, protein kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells was seen. We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicate that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation.
37.	Ghosh, Fredrik, et al. (author) Protein kinase C expression in the rabbit retina after laser photocoagulation. 2005 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 243:8, s. 803-810 Journal article (peer-reviewed)abstract Background: Laser photocoagulation is a well-established treatment for diabetic retinopathy but the mechanism behind its effectiveness has not been elucidated. The protein kinase C (PKC) family is a group of enzymes which has been the subject of extensive interest in clinically related research since the advent of its role in the pathogenesis of diabetic retinopathy. With this study we wanted to explore whether PKC expression is altered in the retina after laser photocoagulation. Methods: Normal rabbit eyes were treated with laser photocoagulation of varying intensity and examined after 30 min to 7 weeks. Treated and untreated regions of the retina were investigated histologically with the MC5 monoclonal antibody against PKC. Labeling for glial fibrillary acidic protein (GFAP), as well as hematoxylin and eosin (H&E) staining was also performed to assess the laser-induced trauma. Results: In the normal retina, the MC5 antibody labeled rod bipolar cells and photoreceptor outer segments corresponding to PKC alpha. A translocated PKC expression with labeling concentrated in the rod bipolar terminals was seen in specimens examined 30 min after laser treatment, and after 1 week, no expression was seen in any part of the retina. After 2 weeks, PKC expression again indicated a translocated labeling pattern. After 5 weeks, labeling was found only in rod bipolar terminals in the peripheral retina. When comparing high- and low-intensity laser treatment 7 weeks postoperatively, no labeling was found in the high intensity-treated retinas, whereas low intensity-treated eyes displayed a near-normal labeling pattern. H&E staining revealed focal neuroretinal edema immediately after laser treatment, also in untreated areas. At later stages, destruction of the outer nuclear layer and migration of pigment epithelial cells in laser-lesioned areas was seen. GFAP-labeled Muller cells were seen 1 week postoperatively in the entire retina. Labeling after this time decreased, but was still present in laser spots after 5 and 7 weeks. Conclusions: Laser photocoagulation alters the expression of PKC in the entire normal rabbit retina. The response follows a temporal pattern and is also related to laser intensity. These findings may help to explain the high efficacy of laser treatment in diabetic retinopathy.
38.	Ghosh, Fredrik, et al. (author) Retinal neuroinflammatory induced neuronal degeneration - Role of toll-like receptor-4 and relationship with gliosis 2018 In: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 169, s. 99-110 Journal article (peer-reviewed)abstract The purpose of this study was to explore retina-intrinsic neuroinflammatory reactions, effects on neuronal survival, relationship with classic gliosis, and possible role of the toll-like receptor 4 (TLR4). To isolate the adult retina from the systemic immune system, a previously described large animal explant culture model was used in which full-thickness porcine retinal sheets can be kept in vitro for extended time periods. Explants were kept for 5 days in vitro (DIV) and were treated with either; lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) inhibitor (CLI-095), LPS + CLI-095, or solvent vehicle throughout the culture period after which retinal sections were examined with hematoxylin and eosin staining and extensive immunohistochemistry. In addition, the culture medium of all explants was assayed for a panel of cytokines at 2 and 5DIV. Compared with in vivo controls, vehicle controls (CT) as well as CLI-095 explants displayed moderate reduction of total thickness and number of retinal neurons with upregulation of glial fibrillary acidic protein (GFAP) throughout the Müller cells. In contrast, LPS and LPS + CLI-095 treated counterparts showed extensive overall thinning with widespread neuronal degeneration but only minimal signs of classical Müller cell gliosis (limited upregulation of GFAP and no downregulation of glutamine synthetase (GS). These specimens also displayed a significantly increased expression of galectin-3 and TGF-beta activated kinase 1 (TAK1). Multiplex proteomic analysis of culture medium at 2DIV revealed elevated levels of IL-1β, IL-6, IL-4 and IL-12 in LPS-treated explants compared to CLI-095 and CT counterparts. LPS stimulation of the isolated adult retina results in substantial neuronal cell death despite only minimal signs of gliosis indicating a retina-intrinsic neuroinflammatory response directly related to the degenerative process. This response is characterized by early upregulation of several inflammatory related cytokines with subsequent upregulation of Galectin-3, TLR4 and TAK1. Pharmacological block of TLR4 does not attenuate neuronal loss indicating that LPS induced retinal degeneration is mediated by TLR4 independent neuroinflammatory pathways.
39.	Ghosh, Fredrik, et al. (author) Selective Removal of Photoreceptor Cells In Vivo Using the Biodegradable Elastomer Poly(Glycerol Sebacate) 2009 In: Tissue Engineering. Part A. - 1937-335X. ; 17:13-14, s. 1675-1682 Journal article (peer-reviewed)abstract Retinal transplantation experiments have advanced considerably during recent years, but remaining diseased photoreceptor cells in the host retina physically obstruct the development of graft-host neuronal contacts which are required for vision. We here report selective removal of photoreceptors using the biodegradable elastomer poly(glycerol sebacate) (PGS). A 1x3 mm PGS membrane was implanted in the subretinal space of normal rabbit eyes, and morphologic specimens were examined with hematoxylin and eosin staining and a panel of immunohistochemical markers. Seven days postoperatively, a patent separation of the neuroretina and retinal pigment epithelium was found as well as loss of several rows of photoreceptors in combination with massive TUNEL staining for apoptosis in the outer nuclear layer. After 28 days, the neuroretina was reattached, the PGS membrane had degraded, and photoreceptors were absent in the implantation area. Activated Müller cells were found in the entire retina in 7-day specimens, and in the implantation area after 28 days. AII amacrine and rod bipolar cell morphology was not affected, except for disrupted dendritic branching which was present in rod bipolar cells in 28-day specimens. We conclude that retinal detachment induced by the biodegradable PGS membrane creates a permissive environment in which graft-host neuronal connections may be facilitated in future retinal transplantation experiments.
40.	Ghosh, Fredrik, et al. (author) Transplantation of full-thickness retina in the normal porcine eye: surgical and morphologic aspects. 2002 In: Retina. - 0275-004X. ; 22:4, s. 478-486 Journal article (peer-reviewed)abstract PURPOSE: To report a surgical technique for transplantation of full-thickness neuroretinal sheets into the subretinal space of a large animal with a vascularized retina and to establish the light microscopic morphology of such specimens. METHODS: Twelve normal pigs underwent transplantation of a neuroretinal sheet from a neonatal donor into the subretinal space by means of a vitrectomy-based technique. After a survival of 33 to 72 days, eye specimens were studied with a light microscope. RESULTS: In most eyes, the transplants displayed a laminated morphology, with photoreceptor outer segments facing the host retinal pigment epithelium. These grafts had normal outer retinal layers, while the inner layers were less developed. The host retina straddling the graft showed evidence of photoreceptor degeneration, but the inner layers were well preserved. CONCLUSION: Full-thickness neuroretinal sheets can be transplanted to the subretinal space of a large animal eye with a vascularized retina. The grafts survive well and display mostly photoreceptors, which in combination with the well-preserved host inner retina may be of importance in attempts at reconstructing the retina in photoreceptor degenerative disease.
41.	Ghosh, Fredrik, et al. (author) Transplantation of full-thickness retina in the rhodopsin transgenic pig. 2004 In: Retina. - 0275-004X. ; 24, s. 98-109 Journal article (peer-reviewed)
42.	Ghosh, Jaydip, et al. (author) Sporulation in mycobacteria 2009 In: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 106:26, s. 10781-10786 Journal article (peer-reviewed)
43.	Ghosh, Jaydip, et al. (author) Sporulation in mycobacteria 2009 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:26, s. 10781-10786 Journal article (peer-reviewed)abstract Mycobacteria owe their success as pathogens to their ability to persist for long periods within host cells in asymptomatic, latent forms before they opportunistically switch to the virulent state. The molecular mechanisms underlying the transition into dormancy and emergence from it are not clear. Here we show that old cultures of Mycobacterium marinum contained spores that, upon exposure to fresh medium, germinated into vegetative cells and reappeared again in stationary phase via endospore formation. They showed many of the usual characteristics of well-known endospores. Homologues of well-known sporulation genes of Bacillus subtilis and Streptomyces coelicolor were detected in mycobacteria genomes, some of which were verified to be transcribed during appropriate life-cycle stages. We also provide data indicating that it is likely that old Mycobacterium bovis bacillus Calmette-Guérin cultures form spores. Together, our data show sporulation as a lifestyle adapted by mycobacteria under stress and tempt us to suggest this as a possible mechanism for dormancy and/or persistent infection. If so, this might lead to new prophylactic strategies.
44.	Ghosh, Moumita, et al. (author) Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages 2011 In: FEBS Letters. - : Elsevier. - 0014-5793 .- 1873-3468. ; 585:4, s. 623-9 Journal article (peer-reviewed)abstract Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up-regulation of lysosomal cathepsins, oxidative stress and ferritin up-regulation, and cell death. Lysosomotropic base NH(4)Cl reduced the ferritin induction and oxidative stress in apoptotic cells induced by MSDH. Cysteine cathepsin inhibitors significantly protected cell death and oxidative stress, but had less effect on ferritin induction. We conclude that oxidative stress induced by lysosomal rupture causes ferritin induction with concomitant mitochondrial damage, which are the potential target for prevention of cellular oxidative stress and cell death induced by typical lysosomotropic substances in different disorders.
45.	Gjörloff, Karin, et al. (author) mfERG in normal and lesioned rabbit retina. 2006 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 244:1, s. 83-89 Journal article (peer-reviewed)abstract Background: To evaluate and describe the cone function in the normal and lesioned rabbit retina using the multifocal electroretinogram (mfERG). Methods: Twelve animals underwent a two-port vitrectomy with subsequent retinectomy in one eye. The area of removed retina was located in the nasal part of the visual streak, and measured approximately 1-2 disc diameters. Both eyes were investigated with mfERG preoperatively and up to 13 weeks postoperatively. A Burian-Allen bipolar contact lens with built-in infrared emitters was used to visualize the retina during the recordings. The averages of the trace array amplitudes in the lower nasal and temporal quadrants were calculated and statistically analyzed at the different time intervals. All eyes were examined histologically with hematoxylin and eosin staining. Results: The retina could be visualized during the mfERG examinations. Postoperatively, up to 3 weeks, amplitudes were reduced over the entire stimulated area in retinectomized eyes (2.20 mu V +/- 1.22 SD) as compared with preoperative examinations (3.40 mu V +/- 1.00 SD). After 7 weeks the amplitudes in the quadrant including the retinectomized area remained low (2.62 mu V +/- 1.02 SD), whereas they were higher than at earlier postoperative examinations in the lower unlesioned temporal quadrant (3.56 mu V +/- 0.71 SD) with a statistical difference between the quadrants. At 13 weeks this was even more pronounced. In unoperated eyes, the area corresponding to the visual streak displayed significantly higher amplitudes than the area superior to the myelinated streak, corresponding well to the cone distribution. High amplitudes were also detected in the area of the myelinated nerve fibers and optic nerve head, most likely as a result of scattering light. In histological sections, the retinectomized area had a diameter of 1-3 mm. Conclusions: This study shows that the mfERG technique can be used as a tool in experimental retinal research involving the rabbit eye, where retinal lesions down to at least 1 mm can be detected. One difficulty involves scattering light emanating from the relatively large optic disc and the myelinated nerve fibers, which makes the use of a mfERG system, in which the fundus can be visualized during stimulation, mandatory.
46.	Gudmundsson, Julius, et al. (author) Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. 2008 In: Nat Genet. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:3, s. 281-3 Journal article (peer-reviewed)
47.	Johansson, Kristina, et al. (author) Tailored vitrectomy and laser photocoagulation without scleral buckling for all primary rhegmatogenous retinal detachments. 2006 In: British Journal of Ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 90:10, s. 1286-1291 Journal article (peer-reviewed)abstract Aim: To investigate the anatomical and functional results and the complications in eyes operated on using vitrectomy without scleral buckling for all forms of rhegmatogenous retinal detachment ( RRD). Methods: All cases of primary RRD at the University Hospital of Lund, Lund, Sweden, treated by one surgeon during a period of 3 years were retrospectively reviewed. In 131 ( 98%) of 134 consecutive cases, a final follow-up record of 3 - 14 months was obtained, and these eyes were included in the study. The surgical protocol was tailored for each case and consisted of vitrectomy, laser photocoagulation and tamponade. Preoperative and intraoperative variables were analyses for risk for redetachment and postoperative proliferative vitreoretinopathy ( PVR). Results: Complete reattachment was achieved in 87% of cases ( 114/131) after one operation and in 95% cases after >= 1 operation. A primary detachment of > 1 quadrant was the only significant risk factor for redetachment ( p < 0.05). The most common cause of redetachment was progressive PVR. Significant risk and factors for PVR postoperatively were a poor preoperative visual acuity and a high number of laser effects during surgery ( p < 0.05). The visual acuity for the total number of eyes, macula-off eyes, and pseudophakic as well as phakic eyes, improved significantly. The visual acuity for macula-on eyes did not change significantly. Six patients developed ocular hypertension and another 6 an epiretinal membrane. Three patients reported a visual field defect. Increased lens opacification was seen in 64 of the 94 ( 68%) phakic eyes. Conclusions: The tailored vitrectomy protocol is well suited to all types of RRD. Increased lens opacification in phakic eyes is common, but visual acuity is considerably improved in phakic as well as pseudophakic eyes. PVR development postoperatively is related to the extent of laser treatment, indicating that the protocol may be even further optimised in the future.
48.	Kjellström, Sten, et al. (author) Alteration of Vitreal Retinoschisin Level in Human Primary Retinal Detachment. 2014 In: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 133:3, s. 353-354 Journal article (peer-reviewed)
49.	Kjellström, Ulrika, et al. (author) Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication : Effect of vigabatrin in the rabbit eye. 2009 In: Graefe's Archive for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 1435-702X .- 0721-832X. ; 247:8, s. 1057-1067 Journal article (peer-reviewed)abstract BACKGROUND: To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. METHODS: Twenty-nine rabbits of mixed strain were divided into two groups, receiving either high-dose (n = 15) or low-dose (n = 14) oral VGB treatment (cumulative dose 29.8 +/- 2.9 g and 14.2 +/- 0.6 g respectively). Ten rabbits receiving water served as control animals. The rabbits underwent three baseline ff-ERG measurements before initiation of VGB medication and two ff-ERG registrations during treatment, after 8 and 12-14 weeks respectively. At the end of the study, the expression of protein kinase C-alpha (PKC-alpha), gamma amino butyric acid (GABA) A receptors, vimentin, glial fibrillary acidic protein (GFAP) and peanut agglutinin (PNA) was examined in retinal sections from all rabbits. RESULTS: In animals of the high-dose group, the ff-ERG measurements revealed a significant decrease of isolated rod b-wave amplitudes, combined rod-cone b-wave amplitudes and amplitudes of oscillatory potentials (OPs); OP1, OP2 and OP3. In the low-dose group, the b-wave amplitudes of combined rod-cone responses as well as OP2 and OP3 were significantly reduced. PKC-alpha labeling demonstrated a dose-related translocation of the enzyme in rod bipolar cells, also revealing a significant decline of the number of PKC-alpha labeled rod bipolar cells in treated animals. Vimentin labeling showed a dose-related deviant labeling pattern of Müller cells, with strikingly low labeling intensity in the outer parts of the cells; in the outer limiting membrane (OLM) as well as the outer nuclear layer (ONL). Labeling with antibodies against GABA A receptors and GFAP, as well as PNA staining, revealed no differences between treated animals and controls. CONCLUSIONS: In this study, VGB medication was associated, in a dose-related manner, with a decrease of ff-ERG amplitudes as well as with altered protein expression in rod bipolar cells and Müller cells, suggesting alterations of inner retinal function. The dose-related morphological and electrophysiological changes indicate a retinal pathology that may explain the constricted visual fields seen in some patients treated with VGB.
50.	Lönngren, Ulrika, 1978- (author) Experimental Injury to the Visual System : Molecular Studies of the Retina 2008 Doctoral thesis (other academic/artistic)abstract Retinal ganglion cells play a crucial role in the relay of visual signals from the eye to the brain. This cell type is affected and eventually lost in the eye disease glaucoma, resulting in progressive and irreversible loss of vision. Studies of the molecular mechanisms leading to retinal ganglion cell death are important for the understanding of the disease and for designing future treatments. This thesis addresses and studies these molecular mechanisms, including alterations in gene expression after experimental retinal injuries. The effects of a neuroprotective drug, brimonidine, after transient retinal ischemia were also studied in order to help explain the mechanisms behind the protective properties of this drug.Several methods, including quantitative reverse transcriptase PCR, micro-arrays, western blot and immunohistochemistry, were used. The results showed that transient retinal ischemia triggers cell division in Müller cells and alters the gene expression of growth factors, their receptors, and intermediate filaments in the retina. Several genes related to the apoptosis process were less affected. Pre-treatment with brimonidine increased the levels of certain growth factors (BDNF, NT3, CNTF, FGF9) compared with vehicle. Brimonidine also had marked effects on genes related to progenitor cells, among them the recognized neural stem cell marker nestin. The increase in levels of nestin after ischemia was countered by brimonidine treatment. Moreover, retinal ganglion cell death following either optic nerve transection or optic nerve crush appears to involve the extrinsic apoptotic pathway although the gene expression response appears to differ between these injuries.The results obtained in this work contribute to an increased understanding of retinal injuries and highlight the importance of Müller cells in the endogenous defense against retinal injuries.

Skapa referenser, mejla, bekava och länka

Permalink

Result 1-50 of 71

Refine your search

Type of publication: journal article (67); doctoral thesis (2); other publication (1); book chapter (1)

Type of content: peer-reviewed (66); other academic/artistic (5)

Author/Editor: Ghosh, Fredrik (62); Arner, Karin (25); Andréasson, Sten (13); Engelsberg, Karl (9); Crafoord, Sven, 1950 ... (7); Barth, Henrik (6); show more...; Ponjavic, Vesna (5); Bruun, Anitha (5); Åkerström, Bo (4); Pritchard, Christoph ... (4); Johansson, Kristina (3); Langer, Robert (3); Malmsjö, Malin (3); Johansson, Kjell (3); Kirsebom, Leif A. (2); Wiklund, Fredrik (2); Thorleifsson, Gudmar (2); Thorsteinsdottir, Un ... (2); Stefansson, Kari (2); Sulem, Patrick (2); Gudmundsson, Julius (2); Agnarsson, Bjarni A. (2); Sigurdsson, Asgeir (2); Benediktsdottir, Kri ... (2); Jakobsdottir, Margre ... (2); Kostic, Jelena (2); Magnusdottir, Dropla ... (2); Ghosh, Shyamali (2); Birgisdottir, Birgit ... (2); Blondal, Thorarinn (2); Bergthorsson, Jon T. (2); Gudbjartsson, Daniel (2); Manolescu, Andrei (2); Kristjansson, Kristl ... (2); Suarez, Brian K. (2); Ober, Carole (2); Gronberg, Henrik (2); Catalona, William J. (2); Einarsson, Gudmundur ... (2); Barkardottir, Rosa B ... (2); Gulcher, Jeffrey R. (2); Kong, Augustine (2); Larsson, Pontus (2); Kjellström, Sten (2); O'Shea, Timothy M. (2); Ghosh, Fredrik K. (2); Abdshill, Hodan (2); Dasgupta, Santanu (2); Bergwik, Jesper (2); Wackenfors, Angelica (2); show less...

University: Lund University (60); Örebro University (11); Uppsala University (3); Linnaeus University (3); Umeå University (2); Linköping University (2); show more...; Karolinska Institutet (2); Mälardalen University (1); show less...

Language: English (71)

Research subject (UKÄ/SCB): Medical and Health Sciences (63); Engineering and Technology (4); Natural sciences (2)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Copy and save the link in order to return to this view