Lens epithelial cells senescence in cataract pathogenesis and emerging therapeutic opportunities

Lens epithelial cells (LECs) senescence is a central pathogenic mechanism in cataract formation, driven by a variety of chronic stressors such as oxidative damage, UV radiation, metabolic disturbances, and mechanical strain. When exposed to these stressors, LECs undergo a series of cellular responses, including stable cell cycle arrest, development of a senescence-associated secretory phenotype (SASP), and impaired autophagic flux. These alterations compromise the function of LECs, disrupt lens homeostasis, and promote the pro-inflammatory microenvironment that accelerates cataract progression. Recent advances in targeting senescent LECs have led to the development of promising pharmacological therapies, including senolytics and senomorphics. Senolytic agents, such as Dasatinib and Quercetin, selectively eliminate senescent cells, while senomorphic agents like Metformin and Rapamycin aim to modulate the senescence-associated secretory phenotype and restore cellular homeostasis. Despite these promising results, challenges remain, particularly in overcoming ocular drug delivery barriers. Nonetheless, the potential of targeting LECs senescence offers new therapeutic opportunities for cataract management. Collectively, these insights support a paradigm shift in cataract management. Rather than relying solely on surgical intervention, future strategies may emphasize biologically informed, disease-modifying, and preventive approaches that target cellular senescence.