Cellular senescence is increased in human retinal microaneurysms during aging

Purpose Different studies indicates that the presence of retinal microaneurysms, dilations of the capillaries which often appear as gross outpouchings of the vessel wall, increases during human aging. However, little is known about the mechanisms that may contribute to the development of these structures. The aim of this study was to examine whether cellular senescence may contribute to the formation of microaneurysms and specifically examine the role of p16INK4a, a cyclin dependent kinase inhibitor, that may act promoting the irreversible cell cycle arrest and senescence. Methods Human retinas were obtained from 14 old-donors and 3 middle-aged donors. p16INK4a expression was analyzed using immunohistochemistry and laser-confocal microscopy. Furthermore, in the same retinas we assessed senescence-associated β-galactosidase (SA-β-gal) activity, a widely used biomarker for cellular sencescence. Results Microaneurysms were present in all the retinas obtained from old donors but were absent in those obtained from midle-aged donors. p16INK4a expression was strongly increased in all retinal layers of old retinas when compared with middle-aged retinas. We observed that p16INK4a expression was increased in retinal blood vessels of aged donors, in which we also detected the presence of high levels of SA-β-gal activity. Furthermore, p16INK4a expression was strickingly increased in retinal microaneuryms when compared with that observed in their associated capillaries. Conclusion p16INK4a was overexpressed in the retinal microaneurysms of aging people indicating that cellular senescence could be a crucial mechanism contributing to the formation of retinal microaneuryms during aging.