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Repetitive stress induces features of accelerated aging in the eye

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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.

The study, titled “Stress-Induced Mouse Eye Aging,” was published today. senescent cellsAlong with her colleagues, Dorota Skowronska-Krawczyk, Ph.D., Assistant Professor of Physiology, Biophysics and Ophthalmology, and faculty member of the Center for Translational Vision Research at the UCI School of Medicine, explores transcriptional and epigenetic events occurring in the aging retina. describes the changes. The team shows how stresses such as elevated intraocular pressure (IOP) in the eye trigger epigenetic transcriptional changes similar to natural aging in retinal tissue. 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. The epigenetic changes we observed suggest a cumulative acquisition of changes in chromatin levels following several instances of stress. This provides an opportunity to prevent blindness if the disease is recognized early. “

Dorota Skowronska-Krawczyk, PhD, Assistant Professor of Physiology and Biophysics and Ophthalmology, Faculty of Translational Vision Research Center, UCI School of Medicine

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 her IOP measurement is often insufficient to characterize the actual pathology and risk of disease progression in patients with glaucoma. 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 elevations 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 therapeutics. We are testing a different approach.”

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 repetitive, mild increases in intraocular pressure. It can accelerate the epigenetic aging of tissues.

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. You can now find the optimal strategy for

This research was funded in part by the National Institutes of Health, the Polish Science Foundation, and the European Union, under the European Regional Development Fund. The authors would like to thank the Blindness Prevention Foundation for UCI Ophthalmology for research support.


Journal reference:

Xu Q. and others. (2022) Stress-induced ocular aging in mice. Senescent cells. doi.org/10.1111/acel.13737.

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