Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), particular, play roles regulating ocular and functions, photoreceptor maturation, maintenance, visual function. Here, we generated organoids (ROs) from human induced pluripotent stem cells differentiated a conditioned medium for 60 days, after which were extracted ROs (Exo-ROs). Subsequently, intravitreally injected the Exo-RO solution into eyes Royal College Surgeons (RCS) rats. Intravitreal administration reduced apoptosis, prevented outer nuclear layer thinning, preserved function RCS RNA sequencing miRNA profiling showed miRNAs mainly mitogen-activated protein kinase (MAPK) signaling pathway. In addition, expression MAPK-related genes proteins was significantly decreased Exo-RO-treated group. These results suggest Exo-ROs may be potentially novel strategy delaying degeneration by targeting MAPK