Professor Emeritus UCLA Los Angeles, California, United States
Abstract: Cell transplantation therapy holds great promise for the treatment of retinal degenerative disorders, such as age-related macular degeneration (AMD) and retinitis pigmentosa. We have generated GMP-grade human retinal pigment epithelial progenitor cell bank (huRPE) by ex vivo expansion of primary human retinal pigment epithelial cells in culture. By performing subretinal transplantation of GMP-grade xeno-free huRPE cell suspensions in MerTK-/- mice and in a NaIO3-induced retinal degeneration monkey model, we demonstrated the rescue effect of huRPE in MerTK-/- mice and its safety in primates. Single-cell RNA sequencing further revealed that these cells exhibit the lowest immunogenicity compared to pluripotent stem cell-derived RPE cells. Based on these preclinical data, we conducted a single-arm exploratory clinical study in seven AMD patients with three different doses of huRPE cells. After 18 months’ follow-up, significant improvement in visual acuity was observed in five out of seven patients. Microperimetry showed the formation of a preferred retinal locus (PRL) at the juxta-scarring area, located at the boundary between normal and atrophic retina. Furthermore, the mERG peak coincided precisely with the PRL, supporting the notion that the improvement in retinal function is mediated by the transplanted RPE, which facilitates the development of a new PRL. Our study demonstrated the feasibility and safety of huRPE transplantation treatment for non-exudative AMD patients.
Funding Source: National Key R&D Program of China (2017YFA0104100, 2017YFC1001300)
