In-vitro effect of aflibercept and dexamethasone on the expression level of genes associated with epithelial-mesenchymal transition in retinal pigment epithelial cells
Purpose: Proliferative vitreoretinopathy (PVR) is the primary cause of surgical failure in retinal detachment repair, and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays a crucial role in the pathophysiology of PVR. The purpose of this study was to investi...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025018523 |
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| Summary: | Purpose: Proliferative vitreoretinopathy (PVR) is the primary cause of surgical failure in retinal detachment repair, and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays a crucial role in the pathophysiology of PVR. The purpose of this study was to investigate the impact of aflibercept, alone and in combination with dexamethasone, on the genes involved in the EMT of RPE cells. Design: In-vitro Study. Methods: RPE cells from passages 5–7 were treated in 5 groups, including 1) bevacizumab, 2) aflibercept, 3) dexamethasone, 4) aflibercept plus dexamethasone, and 5) control group. The expression levels of 6 different EMT-related genes (α-SMA, ZEB1, TGF-β, CD90, β-catenin, and Snail) were measured at 24 h after incubation through real-time PCR. We also assessed morphometric parameters of treated RPE cells using ImageJ software. Results: Gene expression analysis showed that aflibercept reduced α-SMA and ZEB1 expressions by one-fourth compared to the control, while bevacizumab reduced them by half. Treatment with dexamethasone decreased CD90 expression and increased Snail gene expression compared to the control group. Aflibercept plus dexamethasone combination led to a gene expression profile mostly similar to dexamethasone alone. The combination treatment also had a significant increase in β-catenin gene expression. The fold changes in gene expression suggest antagonistic effects of the aflibercept plus dexamethasone combination therapy on α-SMA, ZEB1, and Snail genes, while implying synergistic effects on TGF-β, CD90, and β-catenin. In RPE cells, treatment with dexamethasone decreased both the cell aspect ratio (AR) and cell area compared to the control group. Aflibercept led to a significant but clinically irrelevant decrease in both AR and cell area. When aflibercept was combined with dexamethasone, there was a clinically significant reduction in cell area, but the decrease in AR was unremarkable. Conclusion: Aflibercept may prevent EMT by modulating α-SMA and ZEB-1 gene expression, while dexamethasone mainly affects CD90 gene expression. The combination therapy led to synergistic or antagonistic effects of these medications on distinct EMT genes, which may have clinical implications for the prophylaxis of PVR. |
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| ISSN: | 2405-8440 |