Functional assessment of retinal pigment epithelium cell transplants with various degrees of pigmentation for age-related macular degeneration

Age-related macular degeneration (AMD) is the major cause of blindness and reduced vision among adults in Japan, for which only symptomatic therapy using an anti-vascular endothelial growth factor (anti-VEGF) drug is currently available. Recently, transplantation of retinal pigment epithelium (RPE) cells derived from human embryonic or pluripotent stem cells has been extensively applied in clinical practice as a radical therapy for patients with AMD; however, its therapeutic effect remains limited. RPE cells have melanin pigment granules that increase over time; moreover, the degree of pigmentation (dPG) increases with the number of pigment granules. The expression levels of RPE-specific genes and the secretion of cytokines reportedly increase as dPG increases. In this study, we performed functional characterization of human RPE (h-RPE) cells with low and high dPG to determine which might be suitable for transplantation to patients with AMD. Specifically, we isolated h-RPE cells with low and high dPG based on evaluation of lightness parameters, then characterized these cells separately. Our results showed that RPE cells with low dPG exhibited elevated phagocytosis and cell adhesiveness, as well as reduced VEGF secretion, compared with RPE cells with high dPG. Because these traits are considered preferable for transplantation to patients with AMD, RPE cells with low dPG may be more suitable for transplantation. Cellular senescence (indicated by levels of senescence-related proteins) was more advanced in RPE cells with high dPG, suggesting that cellular senescence is an important factor that contributes to the suitability of RPE cells for transplantation to patients with AMD.

Setoguchi Y, et al