Findings may lead to the development of therapies to prevent damage to the retina, the light-sensitive tissue at the back of the eye.
Boston, Mass. — Chemical eye burns caused by alkali agents not only injure the front of the eye — the cornea, where the contact takes place — but also cause widespread damage to the light-sensitive tissue at the back of the eye (the retina) as well, often leading to optic nerve damage and glaucoma. In a report published online today in the American Journal of Pathology, a research team from Schepens Eye Research Institute of Massachusetts Eye and Ear has identified an inflammatory factor, tumor necrosis factor alpha (TNF-alpha), as the mechanism responsible for causing retinal damage from alkali eye burns.
Chemical eye burns fall into three categories (alkali, acid and corrosive), with burns involving alkali or high pH agents considered the most severe. When alkali chemicals, often found in household cleaning solutions, come into contact with the eye, the pH of the liquid inside the front of the eye rises very rapidly. This in turn causes a massive inflammatory response by the affected tissues. The team’s findings are the first to show that the pH or pressure is not the mediator of retinal damage and that TNF-alpha mediated inflammation is a key driver of neurodegeneration.
“This pH elevation in the aqueous humor causes a massive inflammatory response by the anterior uvea,” said corresponding author Eleftherios I. Paschalis, MSc, PhD, a member of the Boston Keratoprosthesis Laboratory at Mass. Eye and Ear and an Instructor of Ophthalmology at Harvard Medical School. “However, the vitreous humor pH in the retina remains unaffected while levels of TNF-alpha become increased. Our finding suggests that if we can neutralize the TNF-alpha inflammatory response shortly after the injury, perhaps we can stop the whole process and rescue the retina.”
The researchers believe that there may be a window of opportunity to suppress the inflammatory response caused by increased TNF-alpha levels. Before clinical therapies can be developed, however, the researchers must find a way to safely block TNF-alpha without disturbing other natural processes.
To address this challenge, Dr. Paschalis’ team has been developing a novel polymer-based strategy to deliver neutralizing antibodies topically to the eye, without systemic effects. In a recent study, the drug polymer delivered anti-TNF-alpha antibody to an alkali burned rabbit’s eye for 3 months, which resulted in marked suppression of inflammation, improved corneal wound healing, reduced neovascularization and, most importantly, retinal protection. The total dose loaded into the device was very low, thereby reducing the possibility of adverse effects from systemic or high dose exposure to biologics. The study was published in January, 2017 in Investigative Ophthalmology and Visual Science, with Dr. Chengxin Zhou as lead author.
“With this new knowledge regarding the TNF-alpha pathway, we can potentially target the major inflammatory pathway responsible for retinal damage in alkali burns and stop the process before irreparable damage occurs,” said Dr. Paschalis. “If this treatment is successful in humans, then it might be possible to treat other ocular injuries mediated by the TNF-alpha pathway that are known to cause retinal neurodegeneration, such as surgical traumas after penetrating keratoplasty, keratoprosthesis, and autoimmune diseases, such as Steven’s Johnson Syndrome.”
In addition to Dr. Paschalis, authors on the American Journal of Pathology report include co-lead author Chengxin Zhou, Ph.D., and senior author Claes H. Dohlman, MD, PhD, Massachusetts Eye and Ear. Additional co-authors include Fengyang Lei, MD, PhD, Nathan Scott, MD, MPP, Vassiliki Kapoulea, MSc, Marie-Claude Robert, MD, Demetrios Vavvas, MD, PhD, Reza Dana, MD, MPH, MSc, and James Chodosh, MD, MPH. Support for the study includes the Boston Keratoprosthesis Research Fund at Mass. Eye and Ear, the Eleanor and Miles Shore Fund, the Massachusetts Lions Eye Research Fund and Research to Prevent Blindness.
About Massachusetts Eye and Ear
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 2016–2017 “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 New England for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.
About the Harvard Medical School Department of Ophthalmology
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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