Senescent Cells in the Aging of the Lens of the Eye
Age-related cataract formation in the lens of the eye causes blindness. This growing opacity of the lens appears to be driven in large part by a growing burden of cellular senescence in lens cells. Could senolytic therapies to clear senescent cells reduce the need for surgery and the development of cell therapies and tissue engineered replacement lenses? This seems plausible, but cataract are a long way removed from the top of the priority list of conditions that might be beneficially affected by senolytic treatments. It is unclear as to whether any group is working towards clinical trials of senolytics in patients at risk of cataract formation.
Cellular senescence plays a dual role in health and disease, acting as both a guardian against uncontrolled proliferation and a driver of age-related pathologies, including cataract formation. The intricate interplay between oxidative stress, mitochondrial dysfunction, and chronic inflammation underscores the complexity of senescence in lens epithelial cells (LECs), essential for maintaining lens transparency and particularly vulnerable to oxidative stress-induced senescence.
The progressive senescence of LECs represents a critical factor in age-related cataractogenesis. Advances in senotherapeutics may offer promising strategies to mitigate LEC senescence, either by eliminating senescent cells through senolytics or modulating the harmful effects of the senescence-associated secretory phenotype (SASP) with senomorphics. Natural compounds like fisetin, luteolin, and metformin, along with innovative therapies such as FOXO4-DRI and gene editing, highlight the growing potential for targeted interventions to delay cataract progression.
Future research on cellular senescence in cataract formation holds significant potential to uncover novel therapeutic strategies aimed at delaying or preventing lens opacity. A deeper understanding of the molecular drivers of LEC senescence, particularly the role of oxidative stress, mitochondrial dysfunction, and protein aggregation, will be essential for developing targeted interventions. Investigating the interplay between SASP factors and changes in the lens microenvironment could provide insights into how chronic inflammation accelerates cataract progression. Senescence research could pave the way for innovative treatments that preserve lens transparency and prevent age-related cataracts.