Abstract
Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.