Date of Award
January 2017
Document Type
Thesis
Degree Name
Medical Doctor (MD)
Department
Medicine
First Advisor
Lawrence J. Rizzolo
Second Advisor
Ron A. Adelman
Abstract
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.
Recommended Citation
Tainsh, Laurel Tillinghast, "Engineered, Stem Cell-Derived Retinal Tissue For Treating Macular Degeneration In A Porcine Model" (2017). Yale Medicine Thesis Digital Library. 2177.
https://elischolar.library.yale.edu/ymtdl/2177
Comments
This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.