New Study Shows Repeated Stress Accelerates Aging of the Eye

New Study Shows Repeated Stress Accelerates Aging of the Eye

November 22, 2022

According to a new study from the University of California, Irvine, aging plays a significant role in the loss of retinal ganglion cells in glaucoma, and new pathways can be targeted for developing new therapies for glaucoma patients.

The findings were published in Aging Cell.

Dorota Skowronska-Krawczyk, Ph.D., an assistant professor in the departments of physiology & biophysics and ophthalmology and a member of the faculty at the Center for Translational Vision Research at the University of California, Irvine, describes the transcriptional and epigenetic changes occurring in aging retina.

The research team demonstrates how stress, such as increased intraocular pressure (IOP) in the eye, causes epigenetic and transcriptional alterations in retinal tissue that are similar to those associated with aging. And how repeated stress in early retinal tissue induces signs of accelerated aging, such as an accelerated epigenetic age.

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

All cells within an organism are impacted by aging, which is a universal process. In the eye, it is a major risk factor for a group of neuropathies called glaucoma. According to current estimates, there will be approximately 110 million persons with glaucoma (aged 40 to 80) by 2040 as a result of the aging populations around the world.

"Our work emphasizes 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 on the chromatin level are acquired in an accumulative way, following several instances of stress. This provides us with a window of opportunity for the prevention of vision loss, if and when the disease is recognized early."

In people, IOP has a circadian rhythm. It normally oscillates between 12 to 21 mmHg in healthy people, and it tends to be highest for about two thirds of people during the nocturnal period. A single IOP measurement is frequently insufficient to define the real pathology and risk of disease progression in glaucoma patients because of IOP changes.

Long-term IOP fluctuation has been reported to be a strong predictor for glaucoma progression. According to this new study, the tissue's aging is directly caused by the cumulative effect of IOP changes.

"Our work shows that even moderate hydrostatic IOP elevation results in retinal ganglion cell loss and corresponding visual defects when performed on aged animals," said Skowronska-Krawczyk. "We are continuing to work to understand the mechanism of accumulative changes in aging in order to find potential targets for therapeutics. We are also testing different approaches to prevent the accelerated aging process resulting from stress."

Researchers now have a new technique to quantify the effect of stress and treatment on the aging condition of retinal tissue. It was possible for researchers to demonstrate that repetitive, mild IOP elevation can accelerate epigenetic age of the tissues through collaboration with the Clock Foundation and Steve Horvath, Ph.D., from Altos Labs, who invented epigenetic clocks that can measure age based on methylation changes in the DNA of tissues.