Accelerated aging induced by stress in experimental murine ocular hypertension

Abstract

Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited, therefore we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on epigenetic level. We demonstrate that program activated by hypertension is similar to natural aging, and that one of the earliest pathways activated upon stress is senescence. Finally, we show that multiple instances of pressure elevation cause accelerated aging of young retina as measured on transcriptional and epigenetic level. Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related eye-diseases, including glaucoma.