Just like most parts of the human body, our eyes gradually wear out over time. A new study now shows how stress can speed up this aging process, a discovery that could help us tackle eye problems that develop as we age, including the group of vision-loss diseases known as glaucoma .
While the research is based on tests performed on mice, the team believes the same principles are likely to apply to human eyes.
A common consequence of psychological stress even in the healthiest of people is an increase in intraocular pressure (IOP, also known as ocular hypertension), or the pressure of the fluid in the eye. Known to be linked to the development of glaucoma, it appears that the physiological stress of increased IOP may also be linked to markers of biological aging, which can appear as changes in the molecular tags in DNA and proteins that control which genes are turned on or off.
“The epigenetic changes we observed suggest that changes at the chromatin level are acquired in a cumulative manner, after several instances of stress,” says ophthalmologist Dorota Skowronska-Krawczyk, from the University of California, Irvine (UCI) School of Medicine.
“This gives us a window of opportunity to prevent vision loss if and when the disease is recognized early.”
The team looked at the optic nerve head of mouse eyes—the place where retinal cells at the back of the eye converge to form the nerve that goes to the brain—in which IOP had been artificially elevated. In younger mice there was little difference compared to control animals, but in older mice those with mildly elevated eye pressure showed loss of axons or nerve fibers, which also occurs in cases of glaucoma.
To put it another way, older mice appeared more susceptible to changes in pressure in their eyes, which lead to damage caused by inflammation and a gradual loss of cellular function that would normally take years to develop naturally.
In humans, IOP is not constant, but fluctuates throughout the day. More extreme and prolonged fluctuations have previously been associated with the progression of glaucoma, and the researchers behind the new study believe that the cumulative effect of these fluctuations—and the stress they put on the eye—is responsible for tissue aging.
“Our work shows that even modest hydrostatic IOP elevation results in retinal ganglion cell loss and corresponding visual defects when performed in aged animals,” says Skowronska-Krawczyk.
“We continue to work to understand the mechanism of cumulative changes in aging in order to find potential targets for therapeutic purposes. We are also testing different approaches to prevent the accelerated aging process resulting from stress.”
Now that they’ve identified these pressure-induced changes, researchers believe they can use it as a way to assess the epigenetic age of tissue in the eye — the amount of wear and tear, essentially — and thereby make treatments more targeted. and more personalized for individual patients.
In addition to psychological stress, there are several other factors that can cause the pressure inside the eye to increase, from genetics to eye injuries and medications. However IOP is increasing, having a means of studying its effects could save the sight of millions.
As the world’s population ages, glaucoma cases are expected to increase and could reach 110 million by 2040. If left untreated, these conditions can eventually lead to blindness.
While there is no way to completely reverse the damage of glaucoma, it can be treated – and being able to detect it (and the causes that lead to it earlier) would make a significant difference to vision loss.
“Our work highlights the importance of early diagnosis and prevention, as well as age-specific management of age-related diseases, including glaucoma,” says Skowronska-Krawczyk.
The research has been published in Aging cell.