Summary: Retinal vascular diseases, including diabetic retinopathy, affect millions worldwide and are a leading cause of blindness. The retina functions as an extension of the central nervous system and is protected by a highly selective blood–retina barrier that tightly controls what can enter or leave retinal tissue.
This barrier depends on a specialized inner layer of retinal endothelial cells working with pericytes and astrocytes. Because these precise cell types do not form elsewhere in the body, obtaining accurate, consistent human retinal endothelial cells has long been a costly, limited bottleneck for research and regenerative medicine.
A new study reports the first successful derivation of specialized human retinal endothelial cells from induced pluripotent stem cells (iPSCs). Researchers engineered a tailored combination of growth factors that guided common stem-cell–derived endothelial cells to adopt the unique characteristics and functions of retinal vasculature. In animal models of retinal disease, these lab-grown cells integrated into damaged tissue, rebuilt degraded blood vessels, strengthened the blood–retina barrier, and restored retinal function.
Key Facts
- iPSC reprogramming for a renewable cell source: Instead of relying on scarce donor-derived retinal endothelial cells, the team used adult cells reprogrammed into iPSCs to create a scalable, standardized supply of retinal endothelial cells.
- Custom growth factor protocol: Researchers first differentiated iPSCs into general vascular endothelial cells, then applied a precisely formulated cocktail of biochemical growth factors to direct those cells toward a retinal endothelial identity.
- Recreating diabetic retinopathy in vitro: In laboratory microphysiological systems, the iPSC-derived retinal endothelial cells self-assembled into perfusable microvessels. When exposed to hypoxia and high glucose—conditions associated with diabetic retinopathy—these engineered networks broke down in ways that mirror disease progression in patients, creating a human-relevant platform for drug screening.
- Preventive therapeutic integration in vivo: When injected into mouse models with fragile or disorganized retinal vessels, the iPSC-derived cells migrated to injured regions, incorporated into the host vasculature, and formed robust vessels with strengthened barriers before vision loss occurred.
- Commercial and intellectual property status: Supported by both in vitro modeling and in vivo therapeutic results, the research team at Duke University has a patent pending that covers the cell therapy method and the platform for automated drug testing.
Source: Duke University
Biomedical engineers at Duke University have for the first time used human induced pluripotent stem cells to make retinal endothelial cells that match the specialized physiology of eye blood vessels.
Injected into mouse models of retinal disease, these induced retinal endothelial cells integrated with damaged tissue, regenerated blood vessels, and helped restore retinal function. The team also demonstrated that the same cells form functional retinal microvasculature in laboratory models, offering a new route to study and treat eye diseases such as diabetic retinopathy.
Published online June 30 in Nature Biomedical Engineering and supported by the National Eye Institute and NASA funding, the work highlights both a new cellular therapeutic approach and a high-fidelity human model for eye disease research.
“Retinal vascular diseases affect millions of people, yet our limited understanding of the retina’s unique blood vessels hinders development of new treatments,” said Sharon Gerecht, Paul M. Gross Distinguished Professor and Chair of Biomedical Engineering at Duke. “By generating the specific cells that make up retinal blood vessels from human stem cells, we open the door to new therapeutic strategies and research tools.”
The retina is closely linked to the brain: retinal neurons extend directly to the central nervous system, and the retina is guarded by a blood–retina barrier that regulates oxygen, nutrients, water, and drug passage. This barrier is made possible by a tight lining of retinal endothelial cells working with pericytes and astrocytes to form a highly selective vascular interface. Because these endothelial cells are uniquely adapted to the eye environment and do not appear elsewhere, growing or sourcing them has been challenging.
Graduate student Parker Esswein, first co-author on the paper, explained the motivation: “When retinal blood-vessel tissue begins to fail, it causes many disorders that lead to vision loss. Existing sources of retinal endothelial cells are limited and variable. Growing them from iPSCs can reduce cost, increase supply, and improve consistency for research and potential therapies.”
The team used a two-step differentiation strategy. Former PhD student Ying-Yu Lin and Esswein first converted commercial iPSCs into general endothelial cells using established protocols. They then applied a targeted cocktail of growth factors to direct those cells into the retinal endothelial lineage. The resulting cells displayed genetic, protein, and functional features characteristic of retinal endothelium.
Laboratory tests confirmed the cells’ capabilities. In engineered microvascular networks, the induced retinal endothelial cells formed vessel structures and, under hypoxic and high-glucose stress, exhibited barrier breakdown consistent with diabetic retinopathy. In animal studies, injected cells homed to ischemic retinal areas in oxygen-induced retinopathy models, integrated with host vessels, and revascularized damaged tissue.
“These results suggest the cells could serve as both a preventive cell therapy and a robust human model for drug discovery,” Esswein said. The research group plans to further evaluate therapeutic applications and expand industry collaborations to translate these findings from bench to clinic.
Funding: This work was supported by the National Institutes of Health (EY035853), NASA Cooperative Agreement NNX16AO69A via the Translational Research Institute, the National Science Foundation Graduate Research Fellowship Program, and the National Defense Science & Engineering Graduate Fellowship Program.
Key Questions Answered:
A: The retina is part of the central nervous system and is protected by a stringent blood–retina barrier. That barrier relies on retinal endothelial cells that are specialized to the eye and do not form in other tissues, making them difficult to source and replicate for study or repair.
A: The team reprogrammed adult cells into iPSCs, differentiated them into general endothelial cells, then applied a bespoke combination of biochemical growth factors that steered those cells into the retinal endothelial identity.
A: As a test platform, these human retinal endothelial cells form microvascular networks in vitro that reproduce healthy and diabetic conditions, enabling realistic drug testing. As a potential therapy, injected cells integrated into damaged retinas in mice and rebuilt functional vasculature, indicating promise for preventive cell-based treatments.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal article was reviewed in full.
- Additional context was added by the editorial staff.
About this genetics and visual neuroscience research news
Author: Ken Kingery
Source: Duke University
Contact: Ken Kingery – Duke University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modeling” by Ying‑Yu Lin, Parker Esswein, Lucas Ramirez, Emily Warren, Julian Nicenboim & Sharon Gerecht. Nature Biomedical Engineering
DOI: 10.1038/s41551-026-01712-9
Abstract
Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modeling
Retinal microvascular diseases involve compromise of the inner blood–retina barrier (iBRB), a complex structure that remains poorly understood. A renewable source of human iBRB endothelium is essential to advance research and develop therapies.
This study differentiated human iPSCs into retinal endothelial cells (iRECs) by engaging the Wnt–β-catenin pathway, including Norrin–Frizzled4 signaling. The iRECs exhibit genetic, protein, and functional fidelity with unique retinal features.
Injected into oxygen-induced retinopathy mouse models, iRECs integrated into the host vascular network and revascularized ischemic retina. In engineered microphysiological systems, iRECs formed perfusable microvascular networks that reproduce iBRB morphology and phenotype under both healthy and diabetic conditions, and they organized and interacted physiologically with iPSC-derived retinal pericytes.
This work establishes functional human iRECs and microphysiological iBRB models that support mechanistic studies, therapeutic target identification, and strategies to promote revascularization of injured retinas, thereby advancing treatment development.