New findings may pave the way for the development of pharmaceutical therapies to reverse corneal scarring
Boston, Mass. — In cases of severe ocular trauma involving the cornea, wound healing occurs following intervention, but at the cost of opaque scar tissue formation and damaged vision. Recent research has shown that mesenchymal stem cells (MSCs) — which can differentiate into a variety of cells, including bone, cartilage, muscle and fat cells — are capable of returning clarity to scarred corneas; however, the mechanisms by which this happens remained a mystery — until now. In a study published online today in Stem Cell Reports, researchers from Schepens Eye Research Institute of Massachusetts Eye and Ear have identified hepatocyte growth factor (HGF), secreted by MSCs, as the key factor responsible for promoting wound healing and reducing inflammation in preclinical models of corneal injury. Their findings suggest that HGF-based treatments may be effective in restoring vision in patients with severely scarred corneas.
“Our results show that mesenchymal stem cells, in an inflamed environment, secrete high levels of HGF, which inhibit scar formation and restore corneal transparency. But if you silence the HGF expression, the stem cells lose their capacity to inhibit scar formation,” said senior author Sunil K. Chauhan, PhD, an Investigator at Schepens Eye Research Institute of Mass. Eye and Ear and an Assistant Professor of Ophthalmology at Harvard Medical School. “That HGF alone can restore corneal transparency is highly significant, and has tremendous translational implications for developing new treatment modalities.”
Trauma to the eye is the leading cause of corneal opacity, leading to 25 million cases of blindness annually. While injury is not a major cause of blindness, it is one of the most common causes of monocular blindness. Current treatments for corneal scarring vary from topical steroids to corneal transplantation. However, there are limitations to these treatments, including increased risk of infection and rejection of transplants.
With the goal of better understanding why MSCs are capable of restoring clarity to scarred corneas, Schepens Eye Research Institute of Mass. Eye and Ear researchers used an animal model of ocular injury. They observed secretion of high levels of HGF from stem cells at the site of injury. Furthermore, the researchers showed that HGF is solely responsible for the restoration of corneal transparency – an observation that holds promise for developing HGF-based therapy for patients.
“These findings are very exciting, and bring us one step closer to our goal of improving vision in patients with severely damaged corneas following ocular injuries,” said Dr. Chauhan.
Authors on the Stem Cell Reports paper include Drs. Chauhan, Sharad K. Mittal, Masahiro Omoto, Afsaneh Amouzegar, Anuradha Sahu, Alexandra Rezazadeh, Kishore R. Katikireddy, Dhvanit I. Shah, and Srikant K. Sahu of Schepens Eye Research Institute of Massachusetts Eye and Ear/Harvard Medical School. Research supported by grants from the National Institutes of Health and the U.S. Department of Defense.
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Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2015–2016 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in the Northeast for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.
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The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.
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