Overview: Stresses such as increased intraocular pressure in the eye induce transcriptional and epigenetic changes in retinal tissue that are similar to natural aging.
sauce: University of California, Irvine
New research from the University of California, Irvine suggests that aging is a key component of retinal ganglion cell death in glaucoma, and that new pathways can be targeted when designing new treatments for glaucoma patients.
This research is today senescent cellsAlong with her colleagues, Dr. Dorota Skowronska-Krawczyk is an assistant professor of physiology and biophysics and ophthalmology at the UCI School of Medicine and a faculty member at the Center for Translational Vision Research, who has been working on transcriptional and epigenetic changes as they occur. is explained. for aging retinas.
The team shows how stresses such as elevated intraocular pressure (IOP) in the eye trigger epigenetic transcriptional changes in retinal tissue that are similar to natural aging. And how, in young retinal tissue, repetitive stress induces features of accelerated aging, including accelerated epigenetic age.
Aging is a universal process that affects all cells of an organism. In the eye, it is a major risk factor for a range of neurological disorders called glaucoma. Due to the aging population worldwide, current estimates show that the number of people with glaucoma (ages 40-80) will rise to more than 110 million by 2040. I’m here.
“Our work highlights the importance of early diagnosis and prevention and age-specific management of age-related diseases, including glaucoma,” said Skowronska-Krawczyk.
“The epigenetic changes we observed suggest that changes in chromatin levels are cumulatively acquired following several instances of stress. If we do, we have an opportunity to prevent blindness.”
In humans, IOP has a circadian rhythm. In healthy people it typically oscillates between 12 and 21 mmHg, and tends to be highest in about two-thirds of people at night.
Due to IOP variability, a single IOP measurement is often insufficient to characterize the actual pathology and risk of disease progression in glaucoma patients.
Long-term intraocular pressure fluctuations have been reported to be strong predictors of glaucoma progression. This new study suggests that the cumulative effects of intraocular pressure fluctuations are a direct cause of tissue aging.
Skowronska-Krawczyk said, “Our study shows that even moderate hydrostatic IOP increases lead to retinal ganglion cell loss and corresponding visual impairment when performed in aged animals.
“We continue to work to understand the mechanisms of cumulative changes in aging in order to find potential targets for therapeutic interventions. are being tested.”
Researchers now have new tools to estimate the effects of stress and treatment on the aging state of retinal tissue, enabling these new findings. Working with Dr. Steve Horvath of Altos Labs, who pioneered the development of an epigenetic clock that can measure age, researchers were able to demonstrate its repeatability. Mild intraocular pressure elevation can accelerate tissue epigenetic aging.
Skowronska-Krawczyk said, “In addition to measuring visual loss and some structural changes due to stress and potential treatments, we also want to measure the epigenetic age of retinal tissue and use it to prevent aging-induced visual loss. We can find the best strategy for
About this visual neuroscience research news
author: press office
sauce: University of California, Irvine
contact: Press Office – UC Irvine
image: Image credit to UC Irvine
Original research: open access.
“Eye aging in mice due to stress’ Qianlan Xu et al. senescent cells
Overview
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Eye aging in mice due to stress
Aging, a universal process that affects all cells of an organism, is a major risk factor for a range of neurological disorders called glaucoma. In glaucoma, elevated intraocular pressure is one of the known stresses affecting tissues.
Our understanding of the molecular effects of aging on the retinal response to stress is very limited. Therefore, we developed a new mouse model to experimentally approach this question.
Here we show that susceptibility to stress responses increases with age and is primed at the chromatin level.
We show that ocular hypertension activates a stress response that mimics natural aging, accompanied by activation of inflammation and aging.
We show that multiple instances of elevated pressure cause senescence in young retinas as measured by transcriptional and DNA methylation levels, accompanied by changes in local histone modifications.
Our data show that repeated stress accelerates the emergence of tissue senescence functions, suggesting that chromatin modification is a key molecular component of aging.
Finally, our work further emphasizes the importance of early diagnosis and prevention, and age-specific management of age-related diseases, including glaucoma.
