| 1. |
- Agardh, Elisabet, et al.
(författare)
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Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats
- 2000
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Ingår i: Current Eye Research. - 0271-3683. ; 21:1, s. 543-549
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study effects of inhibition of glycation, and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. METHODS: Diabetes was induced in male Wistar rats with streptozocin (STZ; 60 mg/kg BW, i.p.). Diabetic as well as strain matched control rats were fed 1) a normal diet, 2) addition of aminoguanidine in the drinking water (0.5 g/l for diabetic rats and 1.0 g/l for control rats) or 3) probucol in the pellets (1% w/w). After 6 months, the number of acellular vessels, endothelial cells and pericytes were counted in trypsin digested retinal vessel preparations, and the total retinal tissue amount of glutathione (GSH) and cysteine was measured with HPLC. RESULTS: Cataract formation occurred after 13 weeks in diabetic animals compared with 17 weeks for those treated with aminoguanidine, and 16 weeks for those treated with probucol (p < 0.001 in both cases). Aminoguanidine inhibited the formation of acellular collapsed capillary strands, 9 (3-14) vs. 18 (12-262) (median, range) per quadrant in untreated diabetic rats (p = 0.004), while probucol did not have any effect. Neither aminoguanidine, nor probucol influenced the endothelial/pericyte ratio. Diabetes caused a reduction in the GSH/cysteine ratio (10.7 +/- 0.6 vs. 15.3 +/- 1. 5) (mean +/- SD; p < 0.001). Probucol partly restored this imbalance (p < 0.05) whereas aminoguanidine did not. CONCLUSIONS: The results indicate that cataract formation in diabetes involves both glycation and oxidative stress processes. The reduced formation of acellular collapsed capillary strands by aminoguanidine suggests a potential role for glycation in vascular damage. The positive effect of probucol on cysteine/GSH metabolism imbalance indicates that derangements of one of the retinal defense systems against oxidative stress can be normalized by antioxidants.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment
- 1998
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 17:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the levels of the free radical protecting enzyme glutathione and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month-old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus (NIDDM), were examined after a six month period of aminoguanidine treatment. Glutathione levels were measured with high performance liquid chromatography and the endothelial/pericyte ratio was calculated in trypsin digested vessel preparations. RESULTS: The levels of glutathione in GK rat retina were significantly lower compared to controls (p = 0.0108). There was no difference in the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs. 1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte ratio in GK or control rat retina. CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM.
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| 3. |
- Agardh, Elisabet, et al.
(författare)
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Retinal glial cell immunoreactivity and neuronal cell changes in rats with STZ-induced diabetes
- 2001
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 23:4, s. 276-284
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study whether diabetes could influence glial cells, retinal neurons, and pigment epithelial cells and if so, to evaluate whether any changes could be influenced by aminoguanidine (AG) or probucol (PB). METHODS: Streptozocin (STZ)-induced diabetic male Wistar rats and age-matched control rats were fed a normal diet, addition of AG in the drinking water (0.5 g/l for diabetic and 1.0 g/l for control rats) or PB in the pellets (1 % w/w) for one or six months. Paraffin embedded retinal sections were incubated in the primary antibodies GFAP, calbindin, RPE65, and Hu, for glial, horizontal, pigment epithelial, and ganglion cells, respectively, and in fluorescent secondary antibodies. RESULTS: One month after STZ injection, GFAP immunoreactivity was sparse, but after six months it was prominent in glial cells in 5/5 diabetic and 1/7 control retinas (p = 0.015). Neither AG, nor PB influenced this immunoreactivity. Numbers of retinal pigment epithelial cells and cells in the ganglion cell layer, were similar at one and six months of diabetes. By time, the number of horizontal cells decreased (p < 0.001) and branching and numbers of their terminals were reduced (p < 0.001). CONCLUSION: Diabetes for six months resulted in increased glial cell immunoreactivity, and by age, horizontal cell numbers and branching of their terminals decreased, morphological patterns that were unaffected by AG or PB. The numbers of retinal pigment epithelial cells and cells in the ganglion cell layer were unaffected both by age and diabetes.
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| 4. |
- Barth, Henrik, et al.
(författare)
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A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades
- 2021
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 46:3, s. 373-379
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Björkblom, Benny, et al.
(författare)
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Xenobiotic- and Serum-Free Culture of Oral Mucosal Epithelial Cells on Contact Lenses
- 2016
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 41:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/aim: Cultured autologous oral mucosal epithelial cells (OMECs) have proven useful in the treatment of ocular surface disorders. This study is the first to investigate the potential of expanding OMEC in a xenobiotic- and serum-free medium using therapeutic contact lenses (CLs) as a substrate and carrier.Materials and methods: Porcine OMEC were seeded on laminin-coated lotrafilcon A therapeutic CLs with the density of 8x10(4)cells/lens and cultured in a defined serum and xenobiotic-free medium. Confocal immunofluorescence microscopy was used to analyze the following: (1) cellular morphology by using rhodamine-phalloidin staining of F-actin, (2) phenotype by applying antibodies against the progenitor cell marker p63 and the putative stem cell marker ABCG2 and (3) cell viability by using propidium iodide and Hoechst 33342 dual staining.Results: Porcine OMEC attached well to the CLs, and cell-to-cell contacts were evident. After three days in culture, the OMEC displayed a confluent monolayer with uniform cobblestone morphology, whereas stratified cultures with 2-3 layers were formed after six days. No significant difference in expression of p63 was observed after three-day culture (79.414.8%) compared with six-day culture (60.3 +/- 18.9%). ABCG2 expression in the basal cell layer was 6.3 +/- 1.0% and 4.8 +/- 1.8% after three- and six-day culture, respectively. The basal layer viability of cultured OMECs was 99.3 +/- 0.2% and 82.8 +/- 1.1% after three and six days culture, respectively.Conclusions: The use of therapeutic CLs has potential as a substrate and carrier for OMEC cultured in a xenobiotic- and serum-free culture system.
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| 6. |
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| 7. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Intravitreal Injection of Triamcinolone Acetonide into Healthy Rabbit Eyes Alters Retinal Function and Morphology
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:6, s. 649-661
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Tidskriftsartikel (refereegranskat)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.
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| 8. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal function and morphology in rabbit after intravitreal injection of VEGF inhibitors.
- 2012
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:5, s. 399-407
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Tidskriftsartikel (refereegranskat)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.
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| 9. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal Function and Morphology in the Rabbit Eye after Intravitreal Injection of the TNF Alpha Inhibitor Adalimumab.
- 2014
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 39:11, s. 1106-1116
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Tidskriftsartikel (refereegranskat)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.
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| 10. |
- Carlsson, Stina K., et al.
(författare)
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Adenosine A2 receptor presence and synergy with cholinergic stimulation in rabbit lacrimal gland.
- 2010
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Ingår i: Current eye research. - : Informa UK Limited. - 1460-2202 .- 0271-3683. ; 35:6, s. 466-74
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Tidskriftsartikel (refereegranskat)abstract
- Secretion from the lacrimal gland is an important part of the well-being of the eye, and a central part in the search for treatment of dry eye syndrome. Adenosine has stimulatory effects on the lacrimal gland, and can potentiate the effect of the cholinergic agonist carbachol (Cch). The aim of the present study is to investigate the presence of the adenosine A(2) receptor subtypes A(2A) and A(2B) in the rabbit lacrimal gland, and to characterize their role in regulated acinar cell secretion.
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| 11. |
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| 12. |
- Engelsberg, Karl, et al.
(författare)
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Early development of retinal subtypes in long-term cultures of human embryonic retina.
- 2008
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 33:2, s. 185-191
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Tidskriftsartikel (refereegranskat)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.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Ghosh, Fredrik, et al.
(författare)
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Neuronal and Glial Alterations in Complex Long-Term Rhegmatogenous Retinal Detachment.
- 2012
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:8, s. 704-711
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Tidskriftsartikel (refereegranskat)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.
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| 17. |
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| 18. |
- Harun-Or-Rashid, Mohammad, 1980-, et al.
(författare)
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Alpha 2-Adrenergic Receptor Agonist Brimonidine Stimulates ERK1/2 and AKT Signaling via Transactivation of EGF Receptors in the Human MIO-M1 Müller Cell Line
- 2019
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 44:1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Alpha 2-adrenergic receptor (α2-ADR) agonists are used clinically for a range of indications including reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Animal experiments show that α2-ADR agonists attenuate the injury-induced Müller cell dedifferentiation by a mechanism that involves activation and regulation of extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of epidermal growth factor receptors (EGFRs). The purpose of this study was to study and corroborate the activation of this system in human cells.Material and Methods: The human Müller cell line MIO-M1 was treated with the α2A-ADR agonist brimonidine in combination with inhibitors for Src-kinase, EGFR-kinase, matrix metalloproteinase (MMP) as well as small interfering RNAs (siRNAs) for the EGFR. The cells were analyzed using immunocytochemistry, quantitative PCR and western blot techniques.Results: Our results show that human MIO-M1 cells express α2A-ADRs and that stimulation of these receptors caused a robust increase of ERK1/2 and protein kinase B (PKB/AKT) (Thr-308) phosphorylation in MIO-M1 cells. P-ERK1/2 and P-AKT (Thr-308) signaling was mediated by Src-kinase and associated with phosphorylation of tyrosine residue of epidermal growth factor receptor (P-EGFR Y1173). In addition, the agonist caused activation of MMPs. These effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR-kinase inhibitor (AG1478), EGFR-siRNA and a MMP inhibitor (GM6001).Conclusion: The results confirm that this human Müller cell line responds to ADR stimulation with phosphorylation of ERK and AKT, which suggests that it is possible to pharmacologically target ADR to modulate the early events in human Müller cell dedifferentiation in a similar fashion as been shown for chicken Müller cells.Abbreviations: CRALBP: cellular retinaldehyde binding protein; EGFR: epidermal growth factor receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GS: glutamine synthetase; GPCR: G protein-coupled receptor; IR: immunoreactivity; MAPK: mitogen-activated protein kinase; MMP: matrix metalloproteinase; P-ERK1/2: phospho-ERK1/2; qRT-PCR: quantitative reverse transcriptase PCR
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| 19. |
- Huang, Hu, et al.
(författare)
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Association of Placental Growth Factor and Angiopoietin in Human Retinal Endothelial Cell-Pericyte co-Cultures and iPSC-Derived Vascular Organoids
- 2023
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Ingår i: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 48:3, s. 297-311
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Tidskriftsartikel (refereegranskat)abstract
- PurposePlacental growth factor (PlGF) and Angiopoietin (Ang)-1 are two proteins that are involved in the regulation of endothelial cell (EC) growth and vasculature formation. In the retina and endothelial cells, pericytes are the major source of both molecules. The purpose of this study is to examine the association of PlGF and Ang-1 with human EC/pericyte co-cultures and iPSC-derived vascular organoids.MethodsIn this study, we used co-cultures of human primary retinal endothelial cells (HREC) and primary human retinal pericytes (HRP), western blotting, immunofluorescent analysis, TUNEL staining, LDH-assays, and RNA seq analysis, as well as human-induced pluripotent stem cells (iPSC), derived organoids (VO) to study the association between PlGF and Ang-1.ResultsInhibition of PlGF by PlGF neutralizing antibody in HREC-HRP co-cultures resulted in the increased expression of Ang-1 and Tie-2 in a dose-dependent manner. This upregulation was not observed in HREC and HRP monocultures but only in co-cultures suggesting the association of pericytes and endothelial cells. Furthermore, Vascular endothelial growth factor receptor 1 (VEGFR1) inhibition abolished the Ang-1 and Tie-2 upregulation by PlGF inhibition. The pericyte viability in high-glucose conditions was also reduced by VEGFR1 neutralization. Immunofluorescent analysis showed that Ang-1 and Ang-2 were expressed mainly by perivascular cells in the VO. RNA seq analysis of the RNA isolated from VO in high glucose conditions indicated increased PlGF and Ang-2 expressions in the VO. PlGF inhibition increased the expression of Ang-1 and Tie-2 in VO, increasing the pericyte coverage of the VO microvascular network.ConclusionCombined, these results suggest PlGFs role in the regulation of Ang-1 and Tie-2 expression through VEGFR1. These findings provide new insights into the neovascularization process in diabetic retinopathy and new targets for potential therapeutic intervention.
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| 20. |
- Koulikovska, Marina, 1970-, et al.
(författare)
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Platelet Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with Incisional Wound
- 2015
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 40:11, s. 1102-1110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to determine whether platelet rich plasma (PRP) has an effect on corneal stromal cells in a rat model of wound healing following corneal incision. Materials and Methods: The effect of PRP on corneal wound healing in vivo was investigated in a corneal incision wound model in rats. 40 rats were wounded by deep corneal incision, and treated with either topically administered PRP (20 rats) or sodium chloride (20 rats). At 4 hours and 1, 3, and 5 days after incision, α-smooth muscle actin (α SMA), SMAD2 and SMAD3 expression and apoptosis in stromal cells were evaluated by immunohistochemistry, and IL-1β mRNA expression was evaluated by real time PCR.Results: PRP treated corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038, and <0.001, respectively) relative to controls. Interleukin-1β mRNA expression, however, was unchanged in PRP treated corneas relative to controls. Topical PRP treatment resulted in a higher proportion of αSMA-positive myofibroblasts recruited to the wound site relative to control corneas. PRP did not affect activation of SMAD2 but activation of SMAD3 was significantly reduced at day 1 (p=0.001) and dramatically increased at day 5 (p=0.032).Conclusions: PRP treatment resulted in suppressed stromal cell apoptosis followed by SMAD3 activation and a greater proportion of myofibroblasts present at the wound site. Suppression of stromal cell apoptosis after corneal wounding by use of a growth factor rich formulation may lead to myofibroblast accumulation by modulation of the TGF-β pathway.
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| 21. |
- Kronschläger, Martin, et al.
(författare)
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Evolution of TUNEL-labeling in the Rat Lens After In Vivo Exposure to Just Above Threshold Dose UVB
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:8, s. 880-885
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/Aim:To quantitatively analyse the evolution of TUNEL-labeling, after in vivo exposure to UVB.Methods:Altogether, 16 Sprague Dawley rats were unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of ultraviolet radiation in the 300nm wavelength region. Animals were sacrificed in groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye globes were removed and frozen. The frozen eye was cryo-sectioned in 10 mm thick midsagittal sections. From each globe, three midsagittal sections with at least five sections interval in between were mounted on a microscope slide. Sections were TUNEL-labeled and counter stained with DAPI. For quantification of apoptosis, a fluorescence microscope was used. In sections with a continuous epithelial cell surface, the number of lens epithelial cell nuclei and the number of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL-positive epithelial cell nuclei for all three sections of one lens in relation to the total number of epithelial cell nuclei for all three sections of the same lens was compared between exposed and contralateral not exposed lens for each animal.Results:The relative difference of the fraction of TUNEL-positive nuclei between exposed and contralateral not exposed lens increased gradually, peaked in the time interval 5-120 h after exposure, and then declined.Conclusions:Close to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5-120 h after exposure to UVB.
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| 22. |
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| 23. |
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| 24. |
- Lagali, Neil S, 1973-
(författare)
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Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential
- 2020
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Ingår i: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 45:3, s. 278-290
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Forskningsöversikt (refereegranskat)abstract
- The corneal stroma comprises 90% of the corneal thickness and is critical for the corneas transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or re-cellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed.
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| 25. |
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| 26. |
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| 27. |
- Petersen, Anne, 1962, et al.
(författare)
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The proteasome and intracellular redox status: implications for apoptotic regulation in lens epithelial cells.
- 2007
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Ingår i: Current eye research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 32:10, s. 871-82
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to investigate redox regulation of the proteasome as well as the effect of proteasome inhibition on intracellular oxidative status and apoptosis. Methods: Oxidative stress was induced in cultured human lens epithelial cells (HLECs) and intact mouse lenses by 100 mu M H(2)O(2). HLECs were also exposed to the reduced and the oxidized forms of glutathione (GSH/GSSG) and the reducing agent dithiotreitol (DTT). The chymotrypsin-like, the trypsin-like, and the peptidylglutamyl peptidase activities of the proteasome were measured using synthetic fluorogenic substrates. Superoxide as well as peroxide production, mitochondrial membrane potential, and the level of GSH was measured in HLECs after proteasome inhibition by MG-132 or lactacystin. Apoptosis was determined by measuring caspase-3 activation and by studying apoptotic nuclei after staining with Hoechst 33342. Results: All three peptidase activities of the proteasome were inhibited by 100 mu M H(2)O(2) and by the oxidized form of glutathione (GSSG), whereas the reduced form (GSH) stimulated chymotrypsin-like and peptidylglutamyl peptidase activities in HLECs lysates. Intact mouse lenses exposed to 100 mu M H(2)O(2) exhibited loss of transparency and trends of decreased chymotrypsin-like proteasome activity as well as decreased GSH levels. Inhibition of the proteasome in cultured HLECs caused significant increase in apoptosis and disturbed intracellular redox balance. Simultaneous addition of exogenous GSH completely abolished the increased apoptosis seen after MG-132 treatment. Conclusions: This study supports the hypothesis that intracellular proteolytic and oxidative regulatory systems are tightly coupled. The current data also indicate that apoptosis by proteasome inhibition is mediated through oxidative mechanisms.
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| 28. |
- Robciuc, A., et al.
(författare)
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Ceramides in the pathophysiology of the anterior segment of the eye
- 2013
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Ingår i: Current Eye Research. - : Informa Healthcare. - 0271-3683 .- 1460-2202. ; 38:10, s. 1006-1016
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Sphingolipid (SL) research reached a peak in the past years. Yet this positive trend was not evident for eye research as the relative number of studies centered on SLs is decreasing. Our aim is to encourage the inclusion of SL metabolites in studies of ocular pathophysiology by summarizing recent findings and current awareness concerning ceramides in the anterior segment of the eye.Methods: Review of literature relating to ceramides as bioactive lipids and the extent to which their particular nature was investigated in ocular pathophysiology.Results: Ceramides are rare but indispensable lipids that influence cellular responses through their effects on membrane biophysical properties or direct interaction with target proteins. Their biological significance is increased by variability and adaptability as there are tens of enzymes designed to modulate their function. The eye offers a set of unique environments where ceramides or other SLs have not been extensively studied. Not surprisingly, ceramides were associated with apoptosis in the metabolically active tissues, while little is known about its effects on the biophysical properties of the tears or lens lipids. More so, there are still aspects of the ocular homeostasis control where SLs contribution has not been investigated to date (e. g. pathogen aggression).Conclusions: Ceramides and SL metabolism still receive increasing attention and have proven to be a significant metabolite in many research fields (e. g. cancer, stress response and inflammation) and there are yet many questions that they will aid answer. With the present work, we seek to increase awareness of these lipids also in eye research and to highlight their importance as common regulators of various diseases.
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| 29. |
- Roux, Sandrine Le, et al.
(författare)
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Transforming Growth Factor Beta 1 Modulates the Functional Expression of the Neurokinin-1 Receptor in Human Keratocytes
- 2016
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 41:8, s. 1035-1043
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Transforming growth factor beta 1 (TGF-β1) is a cytokine involved in a variety of processes, such as differentiation of fibroblasts into myofibroblasts. TGF-β1 has also been shown to delay the internalization of the neurokinin-1 receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a truncated form, triggering different cellular responses. SP has been shown to affect important events in the cornea - such as stimulating epithelial cell proliferation - processes that are involved in corneal wound healing and thus in maintaining the transparency of the corneal stroma. An impaired signaling through NK-1 R could thus impact the visual quality. We hypothesize that TGF-β1 modulates the expression pattern of NK-1 R in human corneal stroma cells, keratocytes. The purpose of this study was to test that hypothesis.METHODS: Cultures of primary keratocytes were set up with cells derived from healthy human corneas, obtained from donated transplantation graft leftovers, and characterized by immunocytochemistry and Western blot. Immunocytochemistry for TGF-β receptors and NK-1 R was performed. Gene expression was assessed with real-time polymerase chain reaction (qPCR).RESULTS: Expression of TGF-β receptors was confirmed in keratocytes in vitro. Treating the cells with TGF-β1 significantly reduced the gene expression of NK-1 R. Furthermore, immunocytochemistry for NK-1 R demonstrated that it is specifically the expression of the full-length isotype of the receptor that is reduced after treatment with TGF-β1, which was also confirmed with qPCR using a specific probe for the full-length receptor.CONCLUSIONS: TGF-β1 down-regulates the gene expression of the full-length variant of NK-1 R in human keratocytes, which might impact its signaling pathway and thus explain the known delay in internalization after activation by SP seen with TGF-β1 treatment.
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| 30. |
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| 31. |
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| 32. |
- Selvander, Madeleine, et al.
(författare)
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Naevi Characterization Using Hyperspectral Imaging : A Pilot Study
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Ingår i: Current Eye Research. - 0271-3683.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The prevalence of choroidal naevi is common and has been found to be up to 10%. Little is known regarding the optical properties of choroidal naevi. A novel hyperspectral eye fundus camera was used to investigate choroidal naevi’s optical density spectra in the retina. Methods: In an ophthalmology clinic setting, patients with choroidal naevi were included in the study. Visual acuity and pressure were tested. Following mydriatics, optical coherence tomography and fundus photography were taken as a reference, after which a hyperspectral image with 12 nm spectral resolution at 450–700 nm was taken. The optical density spectra was measured across the area of the naevus. Results: Nine patients with 11 naevi were examined. The visual acuity was not affected by any of the naevi. All the naevi were flat as measured either with the optical coherence tomography and/or on inspection, and only one naevi had a risk factor (orange pigmentation). The Wasserstein distance between the background and the naevi was higher at 695 nm compared to 555 nm (p = .002). The naevi could be grouped into three clusters based on the extracted optical density spectra. Conclusion: Choroidal naevi are better visible in longer wavelengths compared to shorter wavelengths. This finding can be used to contour and follow choroidal naevi. Choroidal naevi expose different optical density spectra that can be grouped into three different clusters. One of these clusters has an optical density spectra resembling the absorption spectra of lipofuscin, which may indicate the content of this pigment.
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| 33. |
- Skiljic, Dragana, 1985, et al.
(författare)
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Effects of 17β-Estradiol on Activity, Gene and Protein Expression of Superoxide Dismutases in Primary Cultured Human Lens Epithelial Cells
- 2018
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Ingår i: Current Eye Research. - : Informa UK Limited. - 1460-2202 .- 0271-3683. ; 43:5, s. 639-646
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Protective effects of estradiol against H 2 O 2 -induced oxidative stress have been demonstrated in lens epithelial cells. The purpose of this study was to investigate the effects of 17β-estradiol (E2) on the different superoxide dismutase (SOD) isoenzymes, SOD-1, SOD-2, and SOD-3, as well as estrogen receptors (ERs), ERα and ERβ, in primary cultured human lens epithelial cells (HLECs). Materia ls and methods: HLECs were exposed to 0.1 µM or 1 µM E2 for 1.5 h and 24 h after which the effects were studied. Protein expression and immunolocalization of SOD-1, SOD-2, ERα, and ERβ were studied with Western blot and immunocytochemistry. Total SOD activity was measured, and gene expression analyses were performed for SOD1, SOD2, and SOD3. Results: Increased SOD activity was seen after 1.5 h exposure to both 0.1 µM and 1 µM E2. There were no significant changes in protein or gene expression of the different SODs. Immunolabeling of SOD-1 was evident in the cytosol and nucleus; whereas, SOD-2 was localized in the mitochondria. Both ERα and ERβ were immunolocalized to the nucleus, and mitochondrial localization of ERβ was evident by colocalization with MitoTracker. Both ERα and ERβ showed altered protein expression levels after exposure to E2. Conclusions: The observed increase in SOD activity after exposure to E2 without accompanying increase in gene or protein expression supports a role for E2 in protection against oxidative stress mediated through non-genomic mechanisms.
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| 34. |
- Spinozzi, Daniele, et al.
(författare)
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Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells
- 2019
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Ingår i: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 44:3, s. 243-249
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/Aim: Evaluating the suitability of bioengineered collagen sheets and human anterior lens capsules (HALCs) as carriers for cultivated porcine corneal endothelial cells (pCECs) and in vitro assessment of the cell-carrier sheets as tissue-engineered grafts for Descemet membrane endothelial keratoplasty (DMEK). Materials and Methods: pCECs were isolated, cultured up to P2 and seeded onto LinkCell (TM) bioengineered matrices of 20 mu m (LK20) or 100 mu m (LK100) thickness, and on HALC. During expansion, pCEC viability and morphology were assessed by light microscopy. ZO-1 and Na+/K+-ATPase expression was investigated by immunohistochemistry. Biomechanical properties of pCEC-carrier constructs were evaluated by simulating DMEK surgery in vitro using an artificial anterior chamber (AC) and a human donor cornea without Descemet membrane (DM). Results: During in vitro expansion, cultured pCECs retained their proliferative capacity, as shown by the positive staining for proliferative marker Ki67, and a high cell viability rate (96 +/- 5%). pCECs seeded on all carriers formed a monolayer of hexagonal, tightly packed cells that expressed ZO-1 and Na+/K+-ATPase. During in vitro surgery, pCEC-LK20 and pCEC-LK100 constructs were handled like Descemet stripping endothelial keratoplasty (DSEK) grafts, i.e. folded like a "taco" for insertion because of challenges related to rolling and sticking of the grafts in the injector. pCEC-HALC constructs behaved similar to the DMEK reference model during implantation and unfolding in the artificial AC, showing good adhesion to the bare stroma. Conclusions: In vitro DMEK surgery showed HALC as the most suitable carrier for cultivated pCECs with good intraoperative graft handling. LK20 carrier showed good biocompatibility, but required a DSEK-adapted surgical protocol. Both carriers might be notional candidates for potential future clinical applications.
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| 35. |
- Sundelin, Staffan, et al.
(författare)
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Lipofuscin accumulation in cultured retinal pigment epithelial cells reduces their phagocytic capacity
- 1998
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 17:8, s. 851-857
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Retinal pigment epithelial (RPE) cells slowly accumulate lipofuscin pigment within their acidic vacuolar apparatus as a result of extra- and/or intralysosomal oxidative alterations of phagocytosed photoreceptor outer segments (POS) with consequent imperfect degradation of these structures. In old age, lipofuscin accumulation may become quite substantial. It has been suggested that pronounced accumulation of lipofuscin is related to decreased RPE function and, possibly, to age-related macular degeneration. The aim of the present investigation was to study whether heavy loading with lipofuscin of RPE acidic lysosomes would affect the further phagocytic ability of the cells.Methods. In the first section of the investigation, cultures of rabbit RPE cells were exposed daily to bovine UV-irradiated POS (artificial lipofuscin) for 4 weeks, resulting in a pronounced lipofuscin accumulation of the cells. Fluorescent latex beads (labelled with a red fluorophore) were added to unloaded control cultures at 0 and 4 weeks after their establishment, and to lipofuscin loaded cells after 4 weeks of feeding with artificial lipofuscin. Cellular amounts of lipofuscin, and their phagocytotic activity, were quantified by static fluorometry measuring lipofuscin-specific and red bead-specific fluorescence, respectively. The intracellular location of the beads was verified by confocal laser scanning microscopy.Results. Unloaded, and thus almost lipofuscin-free, control cells exposed to latex beads showed numerous cytoplasmic particles emitting reddish fluorescence, while few particles were taken up by cells initially loaded with artificial, POS-derived, lipofuscin. Measurement of the latex bead-specific fluorescence showed significantly (p < 0.001) higher levels in unloaded control cells than in lipofuscin-loaded ones.In the second part of the investigation, unloaded control cultures and lipofuscin-loaded cultures were exposed to native bovine Texas Red-X-labelled POS 4 weeks after the establishment of the cultures. Unloaded control cells showed a large number of cytopiasmic POS emitting reddish fluorescence, while fewer POS were phagocytosed by cells loaded with artificial lipofuscin. Measurement of the Texas Red-X-specific fluorescence, thus quantifying the phagocytic ability of the cells, showed significantly (p < 0.001) higher levels in control cells than in lipofuscin-loaded ones.Conclusions. Severe lipofuscin accumulation of RPE cells appears to result in a greatly decreased phagocytic capacity. The resulting reduction in ability to cope with the needs of the overlying photoreceptor cells, in order to eliminate the obsolete tips of their POS, may well be of significance in the development of age-related macular degeneration.
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| 36. |
- Svare, Frida, et al.
(författare)
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Pressure-Related Effects on Homeostatic Müller Cell Proteins in the Adult Porcine in Vitro Retina
- 2024
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Ingår i: Current Eye Research. - 0271-3683. ; 49:3, s. 303-313
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore early pressure-related effects on Müller cell homeostatic proteins in the in vitro adult porcine retina. Methods: Retinal explants were subjected to 0-, 10-, 30-, or 60-mmHg of pressure for 24 or 48 h in culture. Retinal explants fixed immediately after enucleation were used as controls. Müller cell proteins were evaluated by GFAP, GS, CRALBP, and bFGF immunohistochemistry. Results: GFAP-labeling revealed no differences in fluorescence intensity after 24 or 48 h in any of the pressure groups compared with control retinas. However, a higher intensity was found in the 30- and 60-mmHg groups compared with 0-mmHg counterparts after 24 and 48 h. A higher intensity in GS-labeled sections was found in the 10-and 60-mmHg groups compared with controls and remaining pressure groups after 48 h. Compared with control retinas, CRALBP labeling revealed a higher intensity in the 60-mmHg group after 24 h and in the 10-, 30-, and 60-mmHg groups after 48 h. After 24 and 48 h, a lower intensity was found in bFGF-labeled cells in the 0-, 10-, and 30-mmHg groups compared with controls, while no difference was seen for the 60-mmHg group. Conclusions: Müller cells in the cultured porcine adult retina respond early to pressure by altering the expression of GFAP as well as the homeostatic proteins GS, CRALBP, and bFGF.
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| 37. |
- Taylor, Linnéa, et al.
(författare)
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Effects of Glial Cell Line-derived Neurotrophic Factor on the Cultured Adult Full-thickness Porcine Retina.
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:4, s. 503-515
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: The tissue culture system offers a possibility to study factors involved in neuronal survival which may be important in a transplantation paradigm. The use of adult tissue in this setting poses specific challenges since traditionally mature neurons survive poorly in vitro. In the current paper, we have explored effects of glial cell line-derived neurotrophic factor (GDNF) on cultures of adult porcine retina. Methods: Full-thickness retinal sheets were isolated from adult porcine eyes and were cultured for 5 or 10 days under standard culture conditions with or without GDNF added to the culture medium. The grafts were analyzed morphologically using hematoxylin and eosin staining, immunohistochemistry and transferase dUTP nick end labeling (TUNEL) labeling. Retinas derived from normal adult porcine eyes were used as controls. Results: After 5 d in vitro (DIV), cultures without GDNF showed dissolving retinal lamination while specimens cultured with GDNF displayed the normal laminated morphology. At 10 DIV, the untreated cultures had been reduced to a degenerated cell mass, while the GDNF-cultured specimens retained thin but distinguishable retinal layers. TUNEL labeling confirmed these results. Immunohistochemical labelings and outer nuclear layer thickness measurements showed an increased preservation of photoreceptors and horizontal cells in the GDNF-treated group. Conclusions: The procedure of culturing retina involves several steps causing severe traumatic effects on the tissue, such as ganglion cell axotomy, interruption of the blood flow as well as separation from the retinal pigment epithelium (RPE). In this paper, we have shown that addition of GDNF in the culture medium attenuates the effect of these steps, resulting in enhanced preservation of several retinal neuronal subtypes. The results may be of importance for research in retinal transplantation where storage time of the donor tissue prior to transplantation is a critical issue.
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| 38. |
- Taylor, Linnéa, et al.
(författare)
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First Responders: Dynamics of Pre-Gliotic Müller Cell Responses in The Isolated Adult Rat Retina.
- 2015
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 40:12, s. 1245-1260
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: To explore the early reactions of the retinal Müller glia in response to retinal insult prior to gliotic remodeling and the sustained upregulation of intermediate filament glial fibrillary acidic protein (GFAP), which has traditionally been considered the most sensitive early indicator of reactive gliosis. Methods: To study pre-gliotic events, we used a model of adult rat retinal explants and related the dynamic expression of GFAP as well as apoptosis, to four key regulators of retinal homeostasis (glutamine synthetase (GS), cellular retinaldehyde binding protein (CRALBP), basic fibroblast growth factor (bFGF), carbonic anhydrase II (CAII)) using immunohistochemistry. Results: We found that a sustained GFAP upregulation couple with gliotic remodeling occurred comparatively late and that this phenomenon was preceded by an initial upregulation followed by depletion of GS, CRALBP, bFGF and CAII in retinal Müller cells. The initial increase of the regulatory proteins, seen after 1-12 h, preceded a first phase of moderate apoptosis, and their depletion after 48 h was followed by massive apoptosis and widespread GFAP upregulation in the Müller cells at 5 days. Conclusion: We conclude that, in the explant model, changes in the expression of the four homeostatic regulatory proteins as well as apoptotic cell death precedes sustained GFAP upregulation and reactive gliosis. Müller cell reactivity has been linked to several retinal conditions, and the herein provided novel information on the dynamics of pre-gliotic events in the lesioned retina may help us understand important pathological mechanisms crucial for future therapeutic intervention.
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| 39. |
- Utheim, Tor Paaske, et al.
(författare)
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Microdot Accumulation in the Anterior Cornea with Aging - Quantitative Analysis with in Vivo Confocal Microscopy
- 2020
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Ingår i: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 45:9, s. 1058-1064
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Degenerative microdot deposits in healthy and hypoxic corneas are believed to represent lipofuscin-like material aggregation in the stroma. To accurately assess microdot deposits in a clinical setting, we sought to quantify these deposits for the first time using the non-invasive clinical imaging technique of in vivo confocal microscopy (IVCM). Methods: The corneas of 102 healthy subjects aged 15-88 years were examined by IVCM and microdot density was quantified using a 6-point grading scale by two masked, trained examiners. Microdot density was analyzed with respect to age, sex and stromal depth, and inter-eye and inter-observer differences were evaluated. Results: In healthy subjects, microdot density decreased from the anterior to posterior stroma, with the greatest accumulation observed in the most anterior stroma (subepithelial region). In this region, microdot density correlated strongly with age (P amp;lt; .0001), with increased microdot deposition in older subjects (amp;gt;60 years) relative to younger ones (amp;lt;45 years) (P amp;lt; .001). Microdot density between eyes of the same subject was highly correlated (r = 0.92, P amp;lt; .0001), while no association with sex was noted (P amp;gt;= 0.05). The mean inter-observer difference in microdot assessment was 0.62 +/- 0.09 grades, with a high correlation of grading between observers (r = 0.77, P amp;lt; .0001). Conclusions: IVCM can be used to non-invasively quantify microdot deposits in the subepithelial corneal stroma with good inter-observer reproducibility. Microdot assessment may provide a novel means of quantifying age-related or pathologic degeneration of the corneal stroma in a clinical setting.
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| 40. |
- Van Bergen, Tine, et al.
(författare)
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Heparanase Deficiency Is Associated with Disruption, Detachment, and Folding of the Retinal Pigment Epithelium
- 2021
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 46:8, s. 1166-1170
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Pentosan polysulfate sodium (PPS; Elmiron) is a FDA-approved heparanase inhibitor for the treatment of bladder pain and interstitial cystitis. The chronic use of PPS has been associated with a novel pigmentary maculopathy, associated with discrete vitelliform deposits that exhibit hyperfluorescence, macular hyper-pigmentary spots, and foci of nodular RPE enlargement. Therefore, this study aimed to investigate the retinal morphology of heparanase knockout mice. Material and methods: The retinal morphology of heparanase knock-out and age-matched control wild type mice of 3-, 9- and 15-weeks old was characterized by means of histological evaluation. Immuno-histological stains for RPE65, F4/80 and Ki67 were performed for investigating the RPE, inflammatory and proliferating cells, respectively. Results: Histological analysis showed no changes in age-matched wild-type controls, whereas the eyes of heparanase null mice were characterized by alterations in RPE and neural retina, as manifest by RPE folds and choroidal thickening, detached RPE cells, thickening of the photoreceptor layer and retinal disorganization. The presence of discrete hyperfluorescent foci, however, was absent. The prevalence of the RPE/choroidal changes or protrusions seemed to progress over time and were correlated with more RPE65 signal rather than influx of F4/80- or Ki67-positive cells. These results indicate that the subretinal alterations were mostly RPE driven, without influx of inflammatory or proliferating cells. Conclusions: Our results indicate that heparanase deficiency in the mice leads to RPE folds, choroidal thickening, and retinal disorganization. The presence of discrete hyperfluorescent foci, a key characteristic of the human disease, was not observed. However, it can be concluded that some of the observations in mice are similar to those seen after chronic use of PPS in humans. These findings indicate that the toxicity observed in the presence of heparanase inhibitors is target-related and will preclude the clinical use of heparanase inhibition as a therapeutic intervention.
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| 41. |
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| 42. |
- Yazdani, Mazyar, et al.
(författare)
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Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort
- 2018
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Ingår i: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 43:12, s. 1465-1470
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p amp;lt;= 0.05). Results: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.
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| 43. |
- Zetterberg, Madeleine, 1969, et al.
(författare)
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Gender and Cataract - The Role of Estrogen
- 2015
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 40:2, s. 176-190
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Forskningsöversikt (refereegranskat)abstract
- There is evidence from epidemiologic data that cataract is more common in women than men. This is not solely due to a higher rate of cataract extraction in women, as is the case in the western world, but several population-based studies show that females have a higher prevalence of lens opacities, especially cortical. There is no firm evidence that lifestyle-related factors are the cause of this gender discrepancy. Focus has therefore been directed towards the role of estrogen in cataract formation. Although data on endogenous and exogenous estrogen involvement in cataractogenesis are conflicting, some studies have indicated that hormone therapy may decrease the risk of cataract and thus be protective. It has been hypothesized that the decrease in estrogen at menopause cause increased risk of cataract in women, i. e. not strictly the concentration of estrogen, but more the withdrawal effect. Estrogens are known to exert several anti-aging effects that may explain the longer lifespan in women, including metabolically beneficial effects, neuroprotection, preservation of telomeres and anti-oxidative properties. Since oxidative stress is considered important in cataractogenesis, studies have investigated the effects of estrogens on lens epithelial cells in culture or in animal models. Several investigators have found protection by physiological concentrations of 17 beta-estradiol against oxidative stress induced by H2O2 in cultured lens epithelial cells. Although both main types of estrogen receptors, ER alpha and ER beta, have been demonstrated in lens epithelium, most studies so far indicate that the estrogen-mediated protection in the lens is exerted through non-genomic, i. e. receptor-independent mechanisms, possibly through phosphorylation of extracellular signal-regulated kinase (ERK1/ERK2), a member of the mitogen-activated protein kinase (MAPK)signaling pathway. Further studies are needed, both epidemiologic as to the role of hormone therapies, and laboratory studies regarding molecular estrogen-mediated mechanisms, in order to comprehend the role of estrogens on cataract formation.
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| 44. |
- Zhang, Hui, et al.
(författare)
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Increased catalase levels and hypoxanthine-enhanced nitro-blue tetrazolium staining in rat retina after ischemia followed by recirculation
- 1995
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 14:1, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, using retinal ischemia as a model, we examined if different periods of ischemia and recirculation influenced the generation of reactive oxygen species, i.e. in hydrogen peroxide generation and nitroblue tetrazolium (NBT) reduction. Ischemia was induced for 30 and 90 min by ligation of the optic nerve with the vessels and recirculation was established by removing the ligature. The rats were sacrificed after 15 min or 3 days of recirculation. The retinas were separated from the pigment epithelium for measurements of catalase activity and examination of NBT staining. Compared to controls, the catalase activity was increased after 30 and 90 min of ischemia followed by 15 min of recirculation, and after 90 min of ischemia followed by 3 days of recirculation. As in controls, NBT staining was observed, both after 30 and 90 min of ischemia followed by 15 min of recirculation, in photoreceptors, in both plexiform layers, in some ganglion and glial cells, and, occasionally, in cells in the inner nuclear layer. Opposite to controls, addition of hypoxanthine to the NBT solution resulted in an increased staining in vessels in the inner nuclear layer in retinas subjected to 30 min of ischemia followed by 3 days of recirculation. The increased catalase activity suggests an increased amount of this free radical scavenger after ischemia followed by short-term and long-term recirculation. The hypoxanthine-enhanced NBT staining of blood vessel walls after ischemia followed by long-term recirculation indicates an activation of xanthine oxidase and an increased production of NBT reductants, some of which may represent oxygen free radicals.
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| 45. |
- Åkerström, Bo, et al.
(författare)
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The Role of Mitochondria, Oxidative Stress, and the Radical-binding Protein A1M in Cultured Porcine Retina.
- 2017
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 42:6, s. 948-961
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to explore the relationship between oxidative stress, antioxidant defense, mitochondrial structure, and biomechanical tissue support in the isolated porcine retina.Methods: Full-thickness retinal sheets were isolated from adult porcine eyes. Retinas were cultured for 2 or 48 h using (1) a previously established low-support explant protocol with photoreceptors positioned against the culture membrane (porous polycarbonate) or (2) a high-support procedure developed by our group, apposing the Müller cell endfeet and inner limiting membrane against the membrane. The grafts were analyzed by quantitative polymerase chain reaction (PCR), immunohistochemistry, and transmission electron microscopy (TEM), and culture medium was assayed for the cell damage and oxidative stress markers lactate dehydrogenase and protein carbonyls.Results: In explants cultured with physical support to the inner border, cone photoreceptors were preserved and lactate dehydrogenase levels were reduced, although an initial (2 h), transient, increased oxidative stress was observed. Elevated expression of the antioxidants α1-microglobulin and heme oxygenase-1 was seen in the mitochondria-rich inner segments after 48 h compared to low-support counterparts. Housekeeping gene expression suggested a higher degree of structural integrity of mitochondria in high-support explants, and TEM of inner segments confirmed preservation of a normal mitochondrial morphology.Conclusion: Providing retinal explants with inner retinal support leads to mobilization of antioxidant proteins, preservation of mitochondrial function, and increased cell viability. Consequently, the failure of low-support retinal cultures to mobilize an adequate response to the oxidative environment may play a key role in their rapid demise. These findings shed new light on pathological reactions in biomechanically related conditions in vivo.
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