Abstract: Blindness are consider as a terrifying disease in the world, although some can be treat by surgery or drug deliver. Photoreceptor degeneration diseases, account for 1/4 of the untreatable blindness. These diseases include macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), affects millions of patients world-wide, remain untreatable due to the lack of effective therapies or surgical interventions. Fetus derived retinal progenitor cells (RPCs) hold promise in the clinical trials and animal experiments. However, the clinical application is now limited by issues such as immune rejection, ethical concerns, and limited availability. T cells, widely used in cancer therapy, which not only can easier and safer to harvest compared to other cells, can be massively activated and expanded in vitro, but also foundation for autologous personalized medicine. ESCs/iPSCs has the capacity to self renew, unlimited proliferation in vitro, and differentiate into all cell types in the human body. Here we aim to develop small molecules to covert T cells and ESCs(Embryonic Stem Cells)/iPSCs(Induced Pluripotent Stem Cells) into retinal progenitor-like cells. Direct conversion by chemical cocktail avoid the insertion mutagenesis of virus integration. Demonstrating a non-genetic, small-molecule-based strategy for direct cell fate conversion. Remarkably, after five days of treatment with our small molecule cocktail, T cells exhibited neuronal-like morphology and expressed key RPC markers. Similarly, ESCs/iPSCs displayed early-phase neuronal differentiation and upregulated RPC-associated genes. These findings suggest that small-molecule-induced reprogramming can provide an alternative source of RPCs, potentially overcoming the limitations of current stem cell therapies. In conclusion, this study not only presents a novel, efficient strategy to generate RPCs direct from T cells and ESCs/iPSCs, offering a potential pathway for future treatments of blinding diseases caused by photoreceptor degeneration, but also brings hope to those suffering from vision loss.
