Repeated Stress Accelerates Aging of the Eye


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

Source: U.C. Irvine

New research from the University of California, Irvine, suggests that aging is an important part of retinal ganglion cell death in glaucoma, and that new avenues could be targeted in designing new treatments for glaucoma patients.

The research was published today in Aging cell. Together with her colleagues, Dorota Skowronska-Krawczyk, Ph.D., assistant professor in the Departments of Physiology & Biophysics and Ophthalmology and the faculty of the Center for Translational Vision Research at UCI School of Medicine, describes the transcriptional and epigenetic changes that take place in aging 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 ageing. And how repetitive stress in young retinal tissue causes features of accelerated aging, including accelerated epigenetic age.

Aging is a universal process that affects all cells in an organism. In the eye, it is a major risk factor for a group of neuropathies called glaucoma. Due to the global aging population, current estimates show that the number of people with glaucoma (aged 40-80) will increase to more than 110 million by 2040.

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

“The epigenetic changes we observed suggest that changes at the chromatin level are acquired in an accumulative manner, following several stress events. This gives us an opportunity to prevent vision loss, if and when the disease is recognized early.”

In humans, IOP has a circadian rhythm. In healthy individuals, it typically fluctuates in the range of 12-21 mmHg and is usually highest in about two-thirds of individuals during the nocturnal period.

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

Prolonged IOP fluctuations have 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.

When the UCI-led team examined the optic nerve head that had been treated with mild pressure elevation, they noted that there was no sign of axon loss in the young optic nerve head. However, significant sectoral loss of axons was observed in the optic nerves of old animals, similar to the phenotype commonly observed in glaucoma patients. Credit: UCI School of Medicine

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

“We continue to work to understand the mechanism of accumulating changes in aging to find potential targets for therapies. We are also testing different approaches to prevent the accelerated aging process caused by stress.”

Researchers now have a new tool to estimate the impact of stress and treatment on the aging status 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 methylation changes in the DNA of tissues, researchers were able to demonstrate that repetitive, mild IOP elevation can accelerate the epigenetic aging of the 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 with aging,” said Skowronska-Krawczyk.

About this visual neuroscience research news

Author: Press Office
Source: U.C. Irvine
Contact: Press Service – UC Irvine
Image: The image is credited to UC Irvine

Original research: Open access.
“Stress-Induced Aging in Mouse Eye” by Qianlan Xu et al. Aging cell


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Stress-induced aging in the mouse eye

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 that affect tissue.

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

Here we show that sensitivity to stress response increases with age and is primed at the chromatin level.

We demonstrate that ocular hypertension activates a stress response similar to natural aging, activating inflammation and aging.

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

Our data demonstrate that repetitive stress accelerates the appearance of aging features in tissues and suggests that chromatin modifications are the key molecular components of aging.

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

The Valley Voice
The Valley Voice
Christopher Brito is a social media producer and trending writer for The Valley Voice, with a focus on sports and stories related to race and culture.


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