New research from the University of California, Irvine suggests that aging is an important component of retinal ganglion cell death in glaucoma, and that new pathways may be targeted when developing new treatments for glaucoma patients.
The study, titled “Stress-Induced Aging of the Mouse Eye,” was published today in the Cell aging. Together with her colleagues, Dorota Skowronska Krawczyk, Ph.D., associate professor of the Departments of Physiology and Biophysics and Ophthalmology and faculty member of the Center for Translational Vision Research at the UCI School of Medicine, describes the transcriptional and epigenetic changes that occur in the aging retina. The team shows how stress, such as increased intraocular pressure (IOP) in the eye, induces epigenetic and transcriptional changes in retinal tissue similar to natural aging. And how in young retinal tissues, repetitive stress causes signs of accelerated aging, including accelerated epigenetic aging.
Aging is a universal process that affects all cells of the body. In the eyes, it is a major risk factor for a group of neuropathies called glaucoma. Due to the increasing aging of the population worldwide, current estimates indicate that the number of people with glaucoma (aged 40-80 years) will increase to more than 110 million in 2040.
“Our work highlights the importance of early diagnosis and prevention, as well as treatment of age-related diseases, including glaucoma,” Skawronska-Krauczyk said. “The epigenetic changes we observed suggest that changes at the chromatin level are acquired cumulatively after multiple stress events. This gives us a window of opportunity to prevent vision loss if and when the disease is recognized at an early stage. “
In humans, IOP has a daily rhythm. In healthy people, it usually fluctuates in the range of 12-21 mm Hg. and tends to be highest in about two-thirds of people at night. Because of IOP fluctuations, a single IOP measurement is often insufficient to characterize the true pathology and risk of disease progression in glaucoma patients. Long-term IOP fluctuations have been reported to be a strong predictor of glaucoma progression. This new study shows that the cumulative effect of IOP fluctuations is directly responsible for tissue aging.
“Our work shows that even a moderate hydrostatic increase in IOP leads to loss of retinal ganglion cells and corresponding visual defects when performed in old animals,” Skawronska-Krauczyk said. “We continue to work to understand the mechanism of cumulative changes in the aging process in order to find potential targets for therapeutic agents. We are also testing different approaches to prevent accelerated aging due to stress.”
Researchers now have a new tool for assessing the effects of stress and treatment on the state of aging retinal tissue, which made these new discoveries possible. In collaboration with the Clock Foundation and Altos Labs’ Steve Horvat, Ph.D., who pioneered the development of epigenetic clocks that can measure age based on methylation changes in tissue DNA, researchers were able to show that periodic mild increases in IOP can accelerate epigenetic tissue aging.
“In addition to measuring visual deterioration and some structural changes due to stress and potential treatments, we can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss with aging,” Skawronska-Krauczyk said.
This research was partially funded by the National Institutes of Health, the Polish Science Foundation, and the European Union under the European Regional Development Fund. The authors gratefully acknowledge the support of the UCI Department of Ophthalmology Research Foundation to Prevent Blindness.