New publication from UConn Health researchers demonstrates promising technique for healing damage from dry eye, surgery, and toxin exposure
The cornea - the clear, dome-shaped outer layer of the eye - contains more nerves per surface area than any other tissue in the human body. Its nerve density is 300-600 times that of the skin. These nerves are vital for preserving eye health, sending pain signals to let you know if your eye is at risk from damage from bright light or a foreign object - and reminding you to continuously blink to prevent your eyes from drying out.
This part of the eye is also known for being remarkably quick to heal. It's why laser eye surgery patients can typically return to their daily activities within a day or two, with minimal discomfort.
Still, a small percentage of people experience lasting adverse effects from eye surgery, including chronic dry eye and pain or deficits in pain sensation. Other people experience these symptoms even without having had surgery, as part of the complex condition known as "dry eye." And still others have more serious eye injuries inflicted by exposure to toxic chemicals, whether household cleaning solvents or chemical weapons deployed in a military context.
New research shows a promising new technique for helping the cornea heal itself in all these contexts. The findings are published in the latest issue of the Journal of Neuroscience Research. The investigation was led by two UConn School of Medicine professors: professor of neuroscience Royce Mohan, Ph.D., and assistant professor of neuroscience Paola Bargagna-Mohan, Ph.D.
Five years ago, says Mohan, their lab had the idea to look closely at Schwann cells in the cornea. These cells wrap themselves around nerve cells, forming a protective sheath and helping signals travel along the nerves. The researchers hypothesized that these cells played a key role in healing the cornea and restoring its sensory function.
"The Schwann cell had never actually been explored for what it's made up of," Mohan explains. "And since the cornea is clear, and there are no blood vessels, we reasoned that the Schwann cells in the cornea would be different from those in the vascularized skin."
Mohan's lab set to work isolating these corneal Schwann cells, using a technique called single-cell RNA sequencing analysis to determine what genes they expressed. In the process, they found a gene called DKK1 (Dickkopf WNT signaling pathway inhibitor 1), which researchers had never seen Schwann cells express before.
Excited by this finding, they developed a DKK1 inhibitor that could be topically applied to the eye. Sure enough, they found that this inhibitor helped repair damage from both physical injury (a small incision similar to the one made by a laser eye surgeon) and chemical injury (exposure to nitrogen mustard) in mouse models. These DKK1 inhibitor treated mice regained corneal sensation as the DKK1 inhibitor promoted Schwann cell and axon regeneration in both injury models.
"We are very excited about this as a promising avenue," says Mohan. "No one has ever shown a therapeutic target for Schwann cells in the cornea - other cell types have been targeted and shown to benefit injuries, but the Schwann cell has been neglected for many, many decades."
In addition to the excitement of pushing the boundaries of scientific discovery, these researchers are especially enthusiastic about the possibility for speedy translation into a product that can benefit real human patients and consumers.
A major challenge in the ophthalmic drug delivery field is that it is hard to get a topical solution to stay in the eye.
"When you blink, over 90% of that drug is washed out immediately with the tear fluid," Mohan says. "So the ophthalmic industry has been experimenting with formulations that would allow the drug to better get into the eye, especially into the deeper stromal tissue, where the Schwann cell network is found. That was one of the key innovations we also introduced in this paper - a better way to deliver the drug."
The patent-pending topical formulation developed by Mohan's lab encapsulates the DKK1 inhibitor using micelles. Eventually, when used by humans via eyedrops, this technology would allow the effective delivery of more of the drug without the need for constant reapplication.
"Cornea damage is notoriously difficult to repair, and this work is a promising novel approach to addressing the issue," says Christopher Conners, Ph.D., Director of Licensing for Life Sciences at UConn's Technology Commercialization Services (TCS), who helped evaluate this treatment and develop a strategy for its protection and commercialization. "At TCS, we are proud to support the development of groundbreaking treatments like this that can make a real difference in the lives of patients."
Since Mohan believes that "science needs to put something in patients' hands," he emphasizes that this drug could help people not only improve eye health and comfort, but also preserve vision.
When cornea injuries do not heal properly, they can scar, potentially permanently reducing vision. Mohan is hopeful that this new therapy can help in these cases, when administered during the initial healing period.
For the mouse eyes exposed to nitrogen mustard, Mohan says, "we found the untreated eyes began to scar. … But when treated with the DKK1 inhibitor, we found these eyes to have better clarity. We were achieving the cardinal functions of the cornea: transparency and sensory function."
Nitrogen mustard is chemically similar to sulfur mustard, more commonly known as mustard gas. This infamous chemical weapon was used in World Wars I and II with the intention of blinding soldiers. While it has been prohibited under international law for several decades, there are verified twenty-first-century instances of its use, such as in the Syrian civil war. Thus, understanding how people can heal and recover vision in the event of a mustard gas attack or other toxic chemical exposure is of interest to the Department of Homeland Security, which has supported Mohan's research in this area.
In addition to Mohan and Bargagna-Mohan, the other named authors on this study are or were members of the lab: first authors Michael Li '25 MD and Christian A. Tallo '26 MD, Mary Katherine Eddy (undergraduate University Scholar); Aarush Kolli '24; and Ricky Paramo '23 MD.
Mohan's research on corneal damage has been supported by the National Institutes of Health (National Eye Institute grant R21EY031113 and Office of the Director [OD] grants R21EY032741 and R01EY037664). Mohan also credits support from the Connecticut Lions Eye Research Foundation and the John A. and Florence Mattern Solomon Chair in Vision Biology and Eyes Diseases at the UConn Health Center for enabling this innovation.
