We identified several predicted pioneer factors in the transition between hiPSCs and RPE that are involved in cellular responses to oxygen-containing compounds, such as the iRPE repressors ATF2 and ATF4, ARNT2, CREB3 and CREB3L2, EGR1, EPAS1 (HIF1A), ESRRA (ERR1), HMGA1, and KLF9, which is known to exacerbate hypoxia-induced neo-angiogenic responses relevant to nvAMD and proliferative diabetic retinopathy. This evidence concerns the gene CREB3 and proliferative diabetic retinopathy.