Aging Cell: Repetitive stress accelerates the aging of the eye

A new study from the University of California, Irvine, shows that aging is an important component of retinal ganglion cell death in glaucoma, and new pathways
can be targeted when designing new treatments for glaucoma patients.

Dr.
Dorota Skowronska-Krawczyk describes the transcriptional and epigenetic changes
that occur during retinal aging.
He is an assistant professor in the Department of Physiology, Biophysics, and Ophthalmology at the UCI School of Medicine and a faculty member
at the Center for Translating Vision Research.
The team showed how stress, such as elevated intraocular intraocular pressure (IOP), can cause retinal tissue to undergo epigenetic and transcriptional changes
similar to natural aging.
and, in young retinal tissue, how repeated stress induces features that accelerate 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 neurological diseases known as glaucoma.
Due to the increasing aging of the global population, current estimates suggest that the number of glaucoma patients (40-80 years old) will increase to more than
110 million by 2040.

"Our work highlights the importance of early diagnosis and prevention, as well as age-specific treatment of age-related diseases, including glaucoma
," said Skowronska-Krawczyk.
"The epigenetic changes we observed suggest that changes in chromatin levels are acquired
cumulatively after several periods of stress.
This gives us a window of opportunity to prevent vision loss if the disease is detected early
.
”

In humans, intraocular pressure has a circadian rhythm
.
In healthy individuals, it typically oscillates in the 12-21 mm Hg range, with about two-thirds of individuals tending to peak
during the night.
Due to fluctuations in intraocular pressure, a single intraocular pressure measurement is often insufficient to characterize the true pathology and risk of
disease progression in patients with glaucoma.
Long-term intraocular pressure fluctuations have been reported to be an important predictor
of glaucoma progression.
The new study shows that the cumulative effect of intraocular pressure fluctuations directly contributes to the aging
of tissues.

Skowronska-Krawczyk said: "Our study shows that in older animals, even moderate intraocular pressure elevation leads to retinal ganglion cell loss and corresponding visual defects
.
" "We are continuing our efforts to understand the mechanisms underlying cumulative changes in the aging process in order to find potential therapeutic targets
.
" We are also testing different methods to prevent stress-induced accelerated aging processes
.
”

Researchers now have a new tool to estimate the effects of stress and treatment on the aging state of retinal tissue, which makes these new findings possible
.
In collaboration with the Clock Foundation and Dr.
Steve Horvath from Altos Lab, the researchers have the potential to demonstrate that repeated, slight elevations of IOP can accelerate the epigenetic age of tissues, a pioneer of the epigenetic clock that can measure age
based on methylation changes in tissue DNA.

"In addition to measuring vision loss and some structural changes due to stress and potential treatments, Skowronska-Krawczyk said, "We can now measure the epigenetic age of retinal tissue and use it to find the best strategies
to prevent vision loss during aging.
"

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