01842nas a2200229   4500000000100000000000100001008004100002260001500043653002200058653003000080100001600110700001900126700001800145700001700163700002100180700001900201245012000220856005500340300000900395520119400404022001401598       2026                            d  c2026-06-3010aBiological models10aStem-cell differentiation1 aYing-Yu Lin1 aParker Esswein1 aLucas Ramirez1 aEmily Warren1 aJulian Nicenboim1 aSharon Gerecht00aDerivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modelling  uhttps://www.nature.com/articles/s41551-026-01712-9  a1-223 aRetinal microvascular diseases involve a compromised inner blood–retina barrier (iBRB), which remains poorly understood. A renewable source of human iBRB endothelium is thus vital for advancing eye research and treatment development. Here we differentiated human induced pluripotent stem cells into retinal endothelial cells (iRECs) via the Wnt–β-catenin pathway, namely Norrin–Frizzled4 signalling. These iRECs show genetic, protein and functional fidelity as well as unique retinal features. When injected into oxygen-induced retinopathy mice, iRECs integrated into the host vascular network and revascularized the ischaemic eye, rescuing the tissue. In microphysiological models, iRECs form perfusable microvascular networks that recapitulate iBRB morphology and phenotype in both healthy and diabetic states while also physiologically organizing and interacting with induced pluripotent stem cell-derived retinal pericytes. Our study establishes functional human iRECs and microphysiological iBRB models that facilitate mechanistic studies aimed at identifying therapeutic targets and promoting the revascularization of injured retinas, thereby supporting treatment advancement.  a2157-846X