Human umbilical cord blood-derived exosomes attenuate senescence in trabecular meshwork cells
Aging increases the risk of trabecular meshwork (TM) cell dysfunction and intraocular pressure dysregulation in glaucoma, a leading cause of irreversible blindness. Exosomes derived from umbilical cord blood (UCB-exos) have emerged as promising therapeutic agents for mitigating cellular senescence. In this study, we investigated the effects of UCB-exos on senescent human trabecular meshwork cells (HTMCs) and aging mouse TM tissue. UCB-exos promoted HTMC proliferation while reducing beta-galactosidase activity, p21 expression, and gamma-H2A.X levels, and increasing lamin B1 in both replicative and stress-induced (TGF-beta2 and H2O2) senescence models. RNA sequencing revealed that UCB-exos upregulated key cell cycle-related genes, including CDK1. Mechanistically, UCB-exos delivered miR-26a-5p, which promoted CDK1-dependent cell cycle progression and counteracted cellular senescence. In vivo, intravitreal administration of UCB-exos to aging mouse eyes reprogrammed the transcriptome of aged TM tissue, restoring age-associated gene expression changes in ribosomal and immune response pathways. Notably, UCB-exos reduced the number of senescent Beam A cells and partially restored the cellular composition of the aged TM tissue, shifting the proportions of Beam A, Beam B, and JCT cells toward a more youthful state. These findings demonstrate that UCB-exos exert potent anti-senescence effects on TM cells both in vitro and in vivo, likely by delivering miR-26a-5p to promote CDK1-dependent cell cycle progression, underscoring their therapeutic potential for glaucoma.