Cellular Senescence in Ocular Surface Diseases: Molecular Mechanisms and Therapeutic Perspectives

Cellular senescence is characterized by stable cell-cycle arrest and a senescence-associated secretory phenotype (SASP). Recurrent desiccating, oxidative, ultraviolet, microbial, and immune-mediated insults may induce stress-induced premature senescence (SIPS) in ocular surface tissues. PubMed and Web of Science were searched from database inception to 30 June 2026. Primary human, animal, and in vitro studies were prioritized, and direct evidence of senescence was distinguished from indirect stress-related or SASP-like associations. The p53–p21CIP1–pRB and p16INK4a–pRB pathways mediate senescence-associated cell-cycle arrest. Reactive oxygen species (ROS)–p38 mitogen-activated protein kinase (p38 MAPK) and cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling act as stress-sensing and inflammatory pathways, whereas mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) contribute to SASP and metabolic regulation. Transient senescence may support wound repair and immune clearance, whereas persistent senescence may contribute to epithelial and endothelial dysfunction, tear-film instability, immune dysregulation, fibrosis, and extracellular matrix remodeling. Mechanistic support is strongest in selected experimental models; evidence in several human ocular surface disorders remains associative. Cellular senescence is a context-dependent contributor to ocular surface pathology. Senolytic and senomorphic strategies remain predominantly preclinical and require disease-, cell-, and stage-specific validation.