Individuals with USH experience loss of both hearing and vision. USH is a rare disease; however, the loss of both vision and hearing is particularly debilitating. Considerable effort has gone into the identification of the genetic defects underlying USH, and more than 10 genes have been implicated in the disease. Despite significant advances in our understanding of the function of these genes in the inner ear, we know far less about the normal and pathological functions of USH genes in the retina, primarily because the human USH retinal phenotypes are not present in mouse models of these mutations. The potential to produce a model retina in vitro, from USH patient-derived iPSCs is an attractive next step to both (1) advance our understanding of this disease in the retina, and (2) to use as a screening tool to evaluate the effectiveness of potential therapies, like viral gene therapy. The generation of USH model retinas will allow us to study the pathophysiology of the disease from the very earliest stages. The model will contain (1) a neural retinal organoid (2) a layer of RPE, and (3) perfused vasculature for both the neural retina and RPE. The neural retina and RPE will be derived from patient-derived iPSCs, while the vasculature will be generated from primary fetal human retinal and choroidal endothelial cells. The vessels will be generated in a microfabricated device that allows us to separately establish the RPE and the neural retina, and then the two layers will be placed adjacent to one another. The ability to perfuse the vasculature allows us to maintain the neural retina and RPE in their natural configuration. We predict that perfusion of the RPE and retina through their own microvessel networks will facilitate their differentiation, and reduce cell death that occurs as the retinal organoids mature.
Solution for: NEI 3-D Retina Organoid Challenge (3-D ROC)
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