Repeated stress accelerates eye aging

Summary: Stress such as elevated intraocular pressure in the eye causes retinal tissue to undergo transcriptional and genetic changes similar to normal aging.

source: University of California Irvine

New research from the University of California, Irvine, indicates that aging is an important component of retinal ganglion cell death in glaucoma, and new pathways can be targeted when designing novel therapies for glaucoma patients.

The study was published today in cell aging. Together with her colleagues, Dorota Skowronska-Krawczyk, PhD, assistant professor in the Departments of Physiology, Biophysics, and Ophthalmology and the Faculty of Translational Vision Research Center at the UCLA School of Medicine, describes the transcriptional and epigenetic changes that occur in the aging retina.

The team shows how stress, such as elevated intraocular pressure (IOP) in the eye, causes retinal tissue to undergo genetic and transcriptional changes similar to normal aging. and how repetitive stress in young retinal tissue accelerates aging including accelerated epigenetic age.

Aging is a global 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 increase in population aging worldwide, current estimates are that the number of people with glaucoma (ages 40-80) will rise to more than 110 million in 2040.

“Our work underscores the importance of early diagnosis, prevention as well as management of age-related disease, including glaucoma,” Skowronska-Krawzyk said.

“The epigenetic changes we observed suggest that changes at the chromatin level are acquired in a cumulative manner, after several stressful situations. This offers 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 tends to be highest in about two-thirds of individuals during the nocturnal period.

Because of the variability of IOP, a single IOP measurement is often insufficient to describe the true pathology and risk of disease progression in patients with glaucoma.

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

This shows the optic nerve segments
When the UCI team examined the optic nerve head of an eye that had been treated with mild pressure, they noticed that in the young optic nerve head, there was no sign of axonal loss. However, in the optic nerves of old animals, significant segmental loss of axons was observed similar to a phenotype commonly observed in patients with glaucoma. Credit: UCI Medical School

“Our work shows that even moderate elevation of the hydrostatic core leads to loss of retinal ganglion cells and corresponding visual defects when performed in aged animals,” Skowronska-Krawzyk said.

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

Researchers now have a new tool to estimate the effect of stress and treatment on the aging state of retinal tissue, which made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, Ph.D. , of Altos Labs, which pioneered the development of epigenetic clocks that can measure age based on methylation changes in the DNA of tissues, the researchers were able to show that frequency, mild hypertension 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 for preventing vision loss during aging,” Skowronska-Krawczyk said.

About this research in Visual Neuroscience News

author: press office
source: University of California Irvine
Contact: Press Office – UC Irvine
picture: Image credits to the University of California, Irvine

Original search: open access.
“Aging-induced stress in the mouse eye” by Qianlan Xu et al. cell aging


Summary

See also

This indicates a brain

Aging-induced stress in the mouse eye

Aging, a global process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, in which elevated eye pressure is one of the stresses known to affect tissues.

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

Here we show that susceptibility to stress response increases with age and primes at the chromatin level.

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

We have shown that multiple states of hyperextension cause aging of the juvenile retina as measured at the level of transcription and DNA methylation and are accompanied by local histone modification changes.

Our data show that repetitive stress accelerates the manifestation of senescence traits in tissues and suggest chromatin modifications as key molecular components of senescence.

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

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