Targeting Angiogenesis and Visual Cycle in Age-Related Macular Degeneration: The Role of Stem Cells and Vinpocetine

Purpose The purpose of this study was to evaluate whether bone marrow stem cells (BMSCs), vinpocetine, or their combination can attenuate amyloid-β (Aβ)-induced alterations in angiogenesis and visual cycle gene expression in a cellular model of age-related macular degeneration (AMD). Methods Human retinal pigment epithelium (RPE) cells (ARPE-19) were exposed to Aβ 1-42 for 24h and divided into four groups: (i) co-culture with BMSCs, (ii) treated with vinpocetine, (iii) treated with BMSCs and vinpocetine, and (iv) untreated control. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the mRNA expression levels of angiogenesis-related genes, vascular endothelial growth factor (VEGF-A) and pigment epithelium-derived factor (PEDF), and RPE-associated visual cycle genes: lecithin retinol acyltransferase (LRAT), retinoid isomerohydrolase (RPE65), retinol dehydrogenase 5 (RDH5), retinol dehydrogenase 10 (RDH10), and retinaldehyde-binding protein 1 (RLPB1).  Results Aβ1-42 significantly reduced ARPE-19 cell viability (p=0.002); all treatments significantly restored viability. Aβ1-42 upregulated VEGF-A expression, which was significantly downregulated by all treatments. Although Aβ1-42 slightly increased PEDF expression, all treatments significantly enhanced its upregulation, with the combination therapy showing the greatest effect (p=0.006, 0.010, and 0.002, respectively). Furthermore, Aβ 1-42 induced upregulation of most visual cycle genes was reversed by all treatments. Conclusion Aβ1-42 induces cytotoxicity, angiogenesis, and dysregulation of visual cycle genes in RPE cells in vitro. BMSCs, vinpocetine, and their combination attenuate these effects, supporting a potential role in AMD therapy pending further investigation.