Human retinal organoids have transformed how we study development and disease, but they come with a persistent limitation: they lack vasculature. Without a vascular network, organoids struggle with oxygen and nutrient delivery as they mature, contributing to hypoxia, stress responses, and – critically – loss of vulnerable neuronal populations such as retinal ganglion cells (RGCs). For ophthalmology researchers interested in neuroprotection and regenerative strategies, that bottleneck has been hard to ignore.
Now, a new Cell Stem Cell study reports a striking advance: transiently vascularized human retinal organoids that show improved RGC survival and functional maturation. The study describes a method to generate retinal organoids containing endothelial cells (ECs), offering a closer approximation of in vivo retinal development and a potentially more faithful model for retinal disease mechanisms.
The study authors used human induced pluripotent stem cells (hiPSCs) to create endothelial cells in 2D culture, then integrated these ECs into developing retinal organoids to generate what they describe as vascularized retinal organoids (vROs). Their workflow includes molecular validation (RT-qPCR), immunocytochemistry and immunohistochemistry, flow cytometry, and quantitative vessel analysis using AngioTool. Importantly, the team also assessed hypoxia and functional readouts using multielectrode arrays (MEAs), alongside optogenetic stimulation protocols to probe light-driven activity.
RGC degeneration is a central theme in glaucoma and optic neuropathies, as well as being one of the earliest limitations in long-term retinal organoid culture. In this study, transient vascularization was associated with improved RGC preservation, suggesting that even a temporary endothelial presence may provide essential metabolic or trophic support during key developmental windows.
Having organoids that better recapitulate in vivo retinal physiology could sharpen our ability to model diseases where neurodegeneration and vascular dysfunction intersect – such as diabetic retinopathy, retinal vein occlusion, or ischemic optic neuropathy.
While the vascularization is described as “transient” in the study, the proof-of-concept remains powerful: introducing endothelial biology into retinal organoids may be a key step toward building more realistic retinal tissue platforms for drug screening, gene therapy development, and future regenerative applications.
Now, a new Cell Stem Cell study reports a striking advance: transiently vascularized human retinal organoids that show improved RGC survival and functional maturation. The study describes a method to generate retinal organoids containing endothelial cells (ECs), offering a closer approximation of in vivo retinal development and a potentially more faithful model for retinal disease mechanisms.
The study authors used human induced pluripotent stem cells (hiPSCs) to create endothelial cells in 2D culture, then integrated these ECs into developing retinal organoids to generate what they describe as vascularized retinal organoids (vROs). Their workflow includes molecular validation (RT-qPCR), immunocytochemistry and immunohistochemistry, flow cytometry, and quantitative vessel analysis using AngioTool. Importantly, the team also assessed hypoxia and functional readouts using multielectrode arrays (MEAs), alongside optogenetic stimulation protocols to probe light-driven activity.
RGC degeneration is a central theme in glaucoma and optic neuropathies, as well as being one of the earliest limitations in long-term retinal organoid culture. In this study, transient vascularization was associated with improved RGC preservation, suggesting that even a temporary endothelial presence may provide essential metabolic or trophic support during key developmental windows.
Having organoids that better recapitulate in vivo retinal physiology could sharpen our ability to model diseases where neurodegeneration and vascular dysfunction intersect – such as diabetic retinopathy, retinal vein occlusion, or ischemic optic neuropathy.
While the vascularization is described as “transient” in the study, the proof-of-concept remains powerful: introducing endothelial biology into retinal organoids may be a key step toward building more realistic retinal tissue platforms for drug screening, gene therapy development, and future regenerative applications.
