Date of Award
Medical Doctor (MD)
Lawrence J. Rizzolo
Ron A. Adelman
Cell replacement therapy with induced pluripotent stem cells (iPSCs) is a promising treatment for diseases of retinal degeneration such as Age Related Macular Degeneration (AMD). Despite progress in the ability to derive retinal progenitor cells from pluripotent cell in vitro, the ability to engineer a transplantable retinal tissue remains a challenge and the necessary large animal models in which to study implantation are lacking.
In this study we established the biocompatibility of iPSC derived retinal progenitor cells (RPCs) and human fetal retinal pigment epithelium (hfRPE) with a novel scaffold composed of gelatin, chondroitin sulfate, and hyaluronic acid (GCH). iPSC-RPCs seeded onto GCH scaffolds either as clusters or after dissociation into single cells attached to, proliferated, and differentiated towards a neural retinal fate as evidenced by gene expression and immunohistochemistry. Dissociation of RPC clusters before seeding, however, resulted in a significant decrease in expression of Recoverin, a key photoreceptor marker.
This study also established a model of outer retinal damage in pigs. Argon laser induced outer retinal damage in the porcine visual streak and was detected on histology and multifocal electroretinography (mfERG) at time points immediately after and 10 days after injury. This study laid the groundwork for a pilot study of subretinal GCH scaffold implantation in pigs.
Tainsh, Laurel Tillinghast, "Engineered, Stem Cell-Derived Retinal Tissue For Treating Macular Degeneration In A Porcine Model" (2017). Yale Medicine Thesis Digital Library. 2177.