The versatile roles of retinal pigment epithelium in the pathophysiology of retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that lead to progressive vision loss, with most disease-causing genes expressed in rod photoreceptors and a smaller fraction in retinal pigment epithelium (RPE) cells. The RPE and photoreceptor cells share a symbiotic relationship characterized by close spatial and functional interactions that play a pivotal role in vision. Although the role of RPE is fundamental to the retina, its involvement in retinal pathogenesis, and, in particular, in RP remains underappreciated. In this review, we summarize morphological alterations in the RPE resulting from pathogenic mutations specific to RPE cells, as well as those occurring secondary to photoreceptor degeneration. We provide a comprehensive summary of how mutations in RPE-specific genes play a key role in the pathophysiology of RP. Finally, we discuss the latest therapeutic approaches, including AAV-mediated gene augmentation, RPE cell transplantation, and pharmacological interventions.