Efficient derivation of hiPSC-derived photoreceptor precursor cells and their neuroprotective effects in retinal degeneration

Retinal degenerative diseases such as retinitis pigmentosa (RP) lack effective therapies capable of restoring vision. Photoreceptor precursor cell (PPC) transplantation is a promising regenerative strategy. This study utilized the PPCs efficiently derived from human-induced pluripotent stem cell (hiPSC). The employment of AM580, a chemical compound of oxidatively stable retinoid analogs, facilitated the differentiation of hiPSCs into CRX⁺/LHX4⁺ PPCs with 99.9% purity. Furthermore, the retinal protective effect of PPCs was confirmed by the result of a bi-dimensional increase in intensity and space in the N-methyl-N-nitrosourea-induced RP model. Besides the retinal protective effects, donor PPCs were observed to express rod- and cone-specific markers and to develop CtBP2⁺ presynaptic specializations that were located in close proximity to host bipolar cells. These observations are consistent with the ability of hiPSC-derived PPCs to engage in structural repair processes, supporting further investigation into their potential for treating retinal degeneration.