Retinal Endothelial Cells Derived from Induced Pluripotent Stem Cells Repair Damaged Retinas in Mice
The retina is considered a part of the central nervous system. As is the case for the brain, a barrier of specialized cells surrounding the blood vessels supplying retinal tissue controls the passage of molecules between blood and tissues. This barrier becomes dysfunctional with age and age-related conditions, and leaks inappropriate molecules into retinal tissue to cause further damage and dysfunction. Again, this is very analogous to barrier dysfunction in the brain, and is thought to be a major contributing factor in age-related neurodegeneration and consequent degenerative conditions.
One of the approaches under development for the treatment of damaged retinal tissue, such as in the context of macular degeneration or diabetic retinopathy, is to produce new cells that can replace dead or dysfunctional cells, or otherwise help to improve function via a health profile of secretions. In today's open access paper, researchers report on generation of endothelial cells of the retinal barrier from induced pluripotent stem cells. When introduced into a damaged mouse retina, these cells help to repair tissue and restore a functional vasculature.
Retinal tissue has the highest energy and oxygen usage in the body due to the retina's intense and continuous neuronal activity. This demand leads to a crucial reliance on the inner blood-retina barrier (iBRB) to maintain ocular homeostasis. The iBRB is a specialized anatomical unit composing the vasculature located within the internal retinal layers of the central nervous system. Retinal endothelial cells (RECs) in the iBRB are continuous endothelial cells (ECs) that form tight junctions to regulate the diffusion of small molecules, such as ions and water, across their cell-cell interface.
Dysfunction and vascular leakage of the iBRB have been identified as a hallmark of numerous retinal microvascular diseases, including diabetic retinopathy (DR), the leading cause of blindness and a common pathology found in patients with diabetes mellitus. The breakdown of the iBRB occurs due to prolonged hyperglycaemia exposure, leading to increased permeability of the endothelial barrier and reduced oxygen delivery to the retina, causing ischaemia. As DR progresses, it can eventually lead to bleeding, retinal detachment and irreversible blindness.
In this study we harnessed Wnt-β-catenin signalling to derive RECs from human induced pluripotent stem cells (iRECs) that can generate a continuous endothelial barrier with a characteristic retinal phenotype and genotype as well as iBRB functionality. We established the therapeutic potential of the iRECs for the ischaemic eye using an oxygen-induced retinopathy (OIR) mouse model. When injected into oxygen-induced retinopathy mice, iRECs integrated into the host vascular network and revascularized the ischaemic eye, rescuing the tissue.