Towards experimental therapies for retinal degenerative diseases

This thesis describes part of the preclinical road that is essential in developing experimental therapies for retinal degenerative diseases such as age-related macular degeneration (AMD) and a specific type of retinitis pigmentosa (RPE-RP). The retinal pigment epithelium (RPE) plays a significant role in the pathology of both diseases. Indeed, patients of all ages can be affected by conditions involving (primarily) the RPE. This thesis is focused on RPE disease pathology, illustrated by the complex retinal disease AMD and a specific genetic form of the monogenic disorder RP. Many experimental therapeutic strategies are being developed to treat AMD and RPE-RP; however, gene therapy and cell-replacement therapy can be considered important strategies for these diseases, especially because of the curative nature of these two treatment modalities. In this thesis, we first used a systematic approach to identify and analyze all preclinical studies that have been published regarding RPE cell-replacement strategy to treat retinal degenerative diseases (Chapter 2). We next used a genome-editing technique to create a new animal model for an RPE-RP subtype and characterized the model in-depth (Chapter 3). Additionally, we describe an induced preclinical model for AMD and its in-depth characterization (Chapter 4). As a final step, we describe the generation of a 3D-bio-printed tissue recapitulating the RPE and underlying tissues and its transplantation and integration into rat eyes (Chapter 5).