Repeated stress accelerates aging of the eye

Summary: Stress, such as elevation of intraocular pressure in the eye, causes retinal tissue to undergo transcriptional and epigenetic changes similar to natural aging.

Font: University of California at Irvine

New research from the University of California, Irvine suggests that aging is a major component of retinal ganglion cell death in glaucoma, and that new pathways may be addressed when designing new treatments for glaucoma patients. .

The study was published today in aging cell. Together with her colleagues, Dorota Skowronska‐Krawczyk, Ph.D., assistant professor in the Departments of Physiology and Biophysics and Ophthalmology and faculty in the Center for Translational Vision Research at the UCI School of Medicine, describe the transcriptional changes and epigenetic that occur in the aging of the retina.

The team shows how stress, such as elevation of intraocular pressure (IOP) in the eye, causes retinal tissue to undergo epigenetic and transcriptional changes similar to natural aging. And, how in young retinal tissue, repetitive stress induces characteristics 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 group of neuropathies called glaucoma. Due to the increasing aging of the world population, current estimates show that the number of people with glaucoma (ages 40-80) will increase to more than 110 million by 2040.

“Our work emphasizes the importance of early diagnosis and prevention, as well as age-specific management of age-related diseases, including glaucoma,” Skowronska-Krawczyk said.

“The epigenetic changes that we observed suggest that the changes in the chromatin level are acquired cumulatively, after several cases of stress. This gives us a window of opportunity to prevent vision loss, as long as the disease is recognized early.”

In humans, IOP has a circadian rhythm. In healthy individuals, it typically ranges from 12 to 21 mmHg and tends to be higher in approximately two-thirds of individuals during the night period.

Due to IOP fluctuations, a single IOP measurement is often insufficient to characterize the actual pathology and risk of disease progression in glaucoma patients.

Long-term IOP fluctuation has been reported to be a strong predictor of glaucoma progression. This new study suggests that the cumulative impact of IOP fluctuations is directly responsible for tissue aging.

This shows optic nerve slices.
When the UCI-led team investigated the optic nerve head of eyes treated with mildly elevated pressure, they noted that there were no signs of axon loss in the young optic nerve head. However, significant sectoral loss of axons similar to the phenotype commonly seen in glaucoma patients was observed in the optic nerves of old animals. Credit: UCI School of Medicine

“Our work shows that even moderate elevation of hydrostatic IOP results in retinal ganglion cell loss and corresponding visual defects when performed in elderly animals,” Skowronska-Krawczyk said.

“We are continuing to work to understand the mechanism of cumulative changes in aging in order to find potential targets for therapy. We are also testing different approaches to prevent the accelerated aging process that results from stress.”

The researchers now have a new tool to estimate the impact of stress and treatment on the aging state of retinal tissue, which has made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, Ph.D., of Altos Labs, who pioneered the development of epigenetic clocks that can measure age based on DNA methylation changes in tissues, the researchers were able to demonstrate that mild elevation of IOP can accelerate the epigenetic age of tissues.

“In addition to measuring vision decline and some structural changes due to stress and potential treatment, we can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss in aging.” Skowronska-Krawczyk said.

About this visual neuroscience research news

Author: press office
Font: University of California at Irvine
Contact: Press Office – UC Irvine
Image: Image is credited to UC Irvine.

original research: Open access.
“Stress-induced aging in the mouse eye” by Qianlan Xu et al. aging cell


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Stress-induced aging in mouse eye

Aging, a universal process that affects every cell in an organism, is a major risk factor for a group of neuropathies called glaucoma, in which elevated intraocular pressure is one of the known stresses affecting the tissue.

Our understanding of the molecular impact of aging on the retinal stress response is very limited; therefore, we developed a new mouse model to address this question experimentally.

Here we show that susceptibility to the stress response increases with age and is based on the chromatin level.

We show that ocular hypertension activates a stress response that is similar to natural aging and involves activation of inflammation and senescence.

We show that multiple instances of pressure elevation cause aging of the young retina as measured at the level of DNA and transcriptional methylation and are accompanied by local histone modification changes.

Our data show that repeated stress accelerates the appearance of aging features in tissues and suggest chromatin modifications as the key molecular components of aging.

Lastly, our work further emphasizes the importance of early diagnosis and prevention, as well as age-specific management of age-related diseases, including glaucoma.

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