Dry eye disease alters how the eye’s cornea heals itself after injury – Washington University School of Medicine in St. Louis

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Mouse studies identify genes and proteins that may be targets for therapy

Apte Lab

Patients with what is known as dry eye disease are more likely to have corneal injury than those with healthy eyes. By studying mice, researchers at Washington University School of Medicine in St. Louis found that proteins made by stem cells that regenerate the cornea could be new targets for treating and preventing such injuries.

The study was published online Jan. 2 in the Proceedings of the National Academy of Sciences.

Dry eye disease occurs when the eye cannot provide adequate lubrication with natural tears. People with the common disorder use a variety of drops to replace lost natural tears and keep the eye lubricated, but when the eye is dry, the cornea is more susceptible to injury.

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“We have drugs, but they only work well in 10% to 15% of patients,” said senior investigator Rajendra S. Apte, MD, PhD, Paul A. Sibis Distinguished Professor John F. Hardesty, MD, Department of Ophthalmology and Visual Sciences. “In this research involving genes key to eye health, we have identified potential targets for treatment that look different in dry eye than in healthy eyes. Millions of people around the world — an estimated 15 million in the United States alone — suffer from eye pain and injury as a result of complications and injuries associated with dry eye disease. By targeting these proteins, we may be able to more successfully treat or even prevent those injuries.

The researchers analyzed genes expressed by the cornea in various mouse models — not just dry eye disease, but also diabetes and other conditions. They found that in mice with dry eye disease, the cornea activated gene expression Spark. They also found that higher levels of SPARC protein were associated with better healing.

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“We conducted single-cell RNA sequencing to identify genes important for maintaining corneal health, and we believe that some of them, particularly SPARC, may provide potential therapeutic targets for the treatment of dry eye disease and corneal injury,” First Author Joseph B. Lin, an MD/PhD student in Apte’s lab.

“These stem cells are important and resilient and a key reason corneal transplants work so well,” Apte explained. “If we identify proteins that don’t pan out as therapies to activate these cells in people with dry eye syndrome, we may even be able to transplant engineered limbal stem cells to prevent corneal injury in dry eye patients.”

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