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- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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