In developed countries, retinal degenerative diseases affecting Retinal Pigmented Epithelium (RPE), including Aged-Macular Dystrophy (AMD) and inherited retinal diseases such Retinitis Pigmentosa (RP), are the predominant causes of human blindness worldwide and are responsible for more than 1.5 million cases in France (30 million worldwide). While AMD, the leading cause of blindness in western countries, may originate from complex interactions of genetic and environmental factors, RP is engendered from monogenic mutations and affect a younger population. The neuroretina is a complex structure whose health depends on blood vessels and RPE, each of which is affected differently in the spectrum of retinal disease. At present, despite the scientific advances achieved in the last years, there is no cure for such diseases. Gene therapy to restore functions of RPE is rendered difficult due to the heterogeneity of causal mutations. In this context, we are ambitioning to develop an Advanced Therapy Medicinal Product (ATMP) based on our expertise in tissue engineering and in the manipulation of pluripotent stem cells. This novel Tissue Engineered Product (TEP) consists in RPE cells derived from clinical grade human embryonic stem cells (hESC) disposed on a biocompatible substrate allowing the formation of 3D functional retinal pigmented epithelium, suitable for transplantation. To reach this aim, (i) we will first optimize a Good Manufacturing Process (GMP)-scalable process for industrial manufacturing of the TEP for clinical use. We already set up and validated a reproducible differentiation protocol to generate pure RPE cells from clinically compatible hESC lines. When cultured onto a biocompatible substrate, RPE cells are polarized and functional. The second aspect of our proposal (ii) will be to test the safety and efficacy of our TEP in animal models (rodents and non-human primates). We have already performed functional experiment in the RCS rat, a rodent model of RP, and demonstrated that the TEP treatment leads to better visual performance that an RPE suspension treatment into the subretinal space of RCS rats and that this recovery was maintained for a longer period of time. We will estimate the risk of hESC contamination leading to side effects like teratoma, as well as shedding and toxicity of our TEP in immunodeficient rodents. This is a prerequisite from regulatory agencies for TEP approval before its first-in-man administration. We will validate the surgical approach and the absence of side-effects in non-human primates. Finally (iii), all the manufacturing procedures will be transferred to Contract Manufacturing Organizations (CMO) for manufacturing of the RPE bank and the TEP clinical lots. The preclinical development program proposed here will lay the foundations for clinical studies early 2019.