Researchers Find That Nicotinamide May Help Treat Fibrotic Eye Diseases and Mitigate Vision
Discovery Could Improve Future Treatment for Wound Healing
Nicotinamide, a form of vitamin B3, can inhibit aggressive cell transformations during wound healing and may be key to the development of therapies to treat fibrotic eye diseases that impair vision, according to a new Mount Sinai study published on Thursday, April 2, in Stem Cell Reports.
The findings apply to a condition in which cells in the retinal pigment epithelium, a layer that supports the retina, transform and develop the characteristics of more aggressive cells known as mesenchymal cells. The condition can be triggered by aging, diabetes, or injury to the eye. This causes development of fibrous membranes that resemble damaging cells found in retinal scar tissue, and can lead to retinal detachment.
The researchers found that nicotinamide not only inhibits these cell transformations, but can also reverse that cell transition and slow down the development of eye diseases that may lead to vision loss or blindness.
When applying nicotinamide as a therapy to human adult cells in vitro, the researchers found that the vitamin B derivative slowed down the aggressive cellular transformation and could promote the opposite transition, from mesenchymal to epithelial, helping to preserve the cell’s original identity.
“This is the first study that shows how nicotinamide can inhibit invasive wound healing, but also reverse the development of membranes associated with scar tissue,” said Timothy Blenkinsop, PhD, co-lead investigator of the study and Assistant Professor of Cell, Developmental and Regenerative Biology at the Icahn School of Medicine at Mount Sinai. “This discovery helps evolve our understanding of wound healing, as well as good inflammation versus bad inflammation. Good inflammation essentially nudges the system into a regenerative response, while bad inflammation can create harmful scar tissue formation. This is an exciting time to understand how this compound can be used to treat and reverse not only fibrotic diseases of the retina but other diseases too.”
The researchers also identified epigenetic and molecular changes that occur during the cell transition process. Nicotinamide therapy resulted in widespread changes in the DNA sequence of the cells, eliciting changes in more than 40,000 identified chromosomal regions. The scientists observed that nicotinamide was associated with massive reorganization of the cell patterns, especially with inducing enhancer elements that lead the cell stage change in the retina. It activated regulatory elements in cells, including transcriptional factors that are prominent regulators of cell transformation.
Sally Temple, PhD, co-lead investigator of the study and Scientific Director at Neural Stem Cell Institute, said the study paves the way to develop new forms of treatment for patients. “Now we know the epigenetic landscape that is associated with the changes activated by nicotinamide, which gives deeper insights into cell transformations and provides an opportunity to explore a pathway for new therapeutic approaches for any condition or complication associated with wound healing.”
This work was supported by funding from the National Eye Institute and NYSTEM.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.