GSE212188
Stress induced accelerated aging in mouse eye [ATAC-seq]
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 chromatin level. We demonstrate that program activated by stress caused by ocular hypertension is similar to natural aging and involves activation of inflammation and senescence. Finally, we show that multiple instances of pressure elevation cause accelerated aging of young retina as measured on transcriptional and epigenetic level and is accompanied by changes in chromatin modifications. Our data suggests that molecular mechanism of aging is regulated at the level of epigenetic activation and repression and, therefore, might be modifiable. Lastly, this work further emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related eye-diseases, including glaucoma. Overall design: To understand the chromatin remodeling events that occur after IOP elevation in young and aged retinas, we performed ATAC-seq on retinas isolated two days after the 30 mmHg IOP treatment.  3-month-old bulk retinas (N=6) was set as control group to 18-month-old bulk retinas (N=6) in the natural aging related differential analysis of genome-wide chromatin accessibility in wildtype mouse.  For mice at each age (3 month or 18 month), unilateral untreated retinas (N=3) were set as control group to unilateral IOP (constant 30mmHg IOP for 1 hour) treated retina (N=3) in the intraocular pressure elevation related differential analysis of genome-wide chromatin accessibility in wildtype mouse.