BioProject

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. More...

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: From the RNA-Seq analysis results we observed that recurrent stress on young tissue induced changes in IOP stress response in transcription were similar to aged retina. We then hypothesized that dynamics of H3K27Ac levels in young retinas upon repetitive stress will be similar to aged retinas upon one-time stress. To test this hypothesis we performed ChIP-Seq anti-H3K27Ac antibody. Less...