Human pluripotent stem cells were turned into retinal endothelial cells via Norrin-Frizzled4 Wnt-beta-catenin signaling, producing cells that matched retinal barrier traits and reached about 74% CD31-positive endothelial yield.
In oxygen-induced retinopathy mice, injected iRECs integrated into host vessels, reduced vaso-obliteration and neovascularization by day 17, formed perfusable human-mouse hybrid networks, and lowered retinal permeability versus PBS-treated eyes.
In lab models, the cells built perfusable inner blood-retina barrier networks with stronger barrier function than non-specific endothelial controls, including higher TEER, lower permeability, and retinal transporter activity such as GLUT1 and p-gp.
Under diabetic-retinopathy-like stress—30 mM glucose plus 1% oxygen—iRECs showed disrupted junction proteins, weaker barrier function, and abnormal 3D vascular remodeling, making them more disease-responsive than generic endothelial cells.
The team also paired iRECs with iPSC-derived retinal pericytes in an organ-on-chip system, creating a more physiologic blood-retina barrier model that could support mechanism studies, drug discovery, and future cell therapies.
Beyond repairing vision, how will these 'retina-on-a-chip' models change the discovery of all future eye medicines?
With biotech also targeting the Wnt pathway, is the future of eye repair a cell transplant or a breakthrough drug?
Could this stem cell therapy become the one-time fix that ends the burden of frequent eye injections for patients?
Generating Retinal Endothelial Cells from iPSCs: Transforming Disease Modeling and Therapy for Diabetic Retinopathy (2026)
Overview
In 2026, Duke University researchers achieved a major breakthrough by generating retinal endothelial cells (RECs) from human induced pluripotent stem cells (iPSCs) for the first time, as published in Nature Biomedical Engineering. Using a novel two-step protocol that precisely activates the Wnt–β-catenin pathway, they efficiently guided iPSCs to become highly pure and functional RECs. This advance opens new doors for modeling retinal vascular diseases and developing innovative therapies, marking a significant step forward in both understanding and treating conditions that cause vision loss.