The Biology and Cell Engineering of Retinal Pigment Epithelium Cell Transplantation: Developing a Living Drug

Age-related macular degeneration (AMD) is a multifactorial retinal disease that causes progressive vision loss, with retinal pigment epithelium (RPE) atrophy representing a key initiating event. The RPE monolayer plays a crucial role in maintaining photoreceptor and choriocapillaris health and function. In advanced AMD stages, degeneration extends to the photoreceptors and choriocapillaris, likely as a consequence of preceding RPE atrophy. Existing treatment modalities aim to slow disease progression rather than restore degenerated cells and improve visual function. Pluripotent stem cell-derived RPE cell replacement therapy has emerged as a promising approach for restoring native retinal structure and visual function. This review provides an overview of RPE biology and function, clinical-grade manufacturing of RPE transplants, quality control considerations, and the use of scaffolds to improve delivery and integration. We also summarize preclinical and clinical studies that assess the safety, efficacy, and translational potential of RPE transplantation for AMD and other retinal degenerative conditions.