Research Paper
Eye Diseases and Senescence
Author
Koji Kitazawa, Kohsaku Numa, Sandip Kumar Patel, Christina D. King, Akifumi Matsumoto, Chie Sotozono, Pierre-Yves Desprez, Birgit Schilling and Judith Campisi
Abstract
Aging is a process often associated with various age-related diseases. Senescence is one of the hallmarks of aging, and senescent cells acquire a complex, often pro-inflammatory, secretory phenotype termed the senescence-associated secretory phenotype (SASP). Here we show that ocular surface cells from human cornea become senescent upon X-irradiation, characterized by increased SA-β-gal activity, decreased cell proliferation, increased expression of p16, and disruption of epithelial barrier. Comprehensive transcriptomic and proteomic analysis revealed that human senescent ocular cells acquire a SASP that disrupts epithelial barrier function. During aging in mice, senescent ocular cells accumulate, resulting in decreased epithelial barrier and chronic inflammation. Lacrimal gland excision, which leads to symptoms of dry eye (DE), resulted in corneal opacity associated with severe angiogenesis only in aged mice but not in young mice, and early senolytic treatment protected old DE mice from corneal opacity. In conclusion, senescent cells alter the ocular microenvironment through their SASP and eliminating these cells could represent a potential approach to alleviate symptoms associated with aged ocular surface.