Researchers at Schepens Eye Research Institute of Massachusetts Eye and Ear have shown a link between mitochondrial dysfunction in corneal endothelial cells and the development of Fuchs' Endothelial Corneal Dystrophy. This study, published today in the journal, Antioxidants & Redox Signaling, is the first study to demonstrate that lifelong accumulation of oxidative DNA damage leads to mitochondrial dysfunction and subsequent cell death in the tissue of the corneal endothelium. These changes are the result of free radical-induced molecular changes that are characteristic of FECD.
FECD is an age-related and genetic eye disease that affects up to four percent of the U.S. population over the age of 40 and is becoming more prevalent in women. It is one of the most common causes of corneal swelling and may progress to blindness if left untreated. Currently, corneal transplantation is the only course of treatment to restore lost vision in patients with FECD.
"Our first goal is to identify the cause of cell death in FECD," said Ula Jurkunas, M.D., Principal Investigator on the study, Associate Professor of Ophthalmology at Mass. Eye and Ear and Harvard Medical School (HMS), and Co-Director of the HMS Ophthalmology Cornea Center of Excellence. "This is a significant advancement in that process and moves us one step closer to our ultimate goal, which is to provide FECD patients with alternative and safer treatments options to transplantation."
The function of the corneal endothelium is to keep the cornea clear. Because endothelial cells do not divide in humans, they are very prone to DNA damage from ultraviolet light or from the byproducts of energy production in the mitochondria. In FECD, the underlying genetic defects make the corneal endothelial cells even more susceptible to damage, and eventually cause dysfunction in the mitochondria.
In their study, the researchers detected an increase in mitochondrial and nuclear DNA damage in FECD and correlated the damage with loss of mitochondrial energy production. The result was mitochondrial fragmentation followed by release of cytochrome c, a small protein associated with the inner membrane of the mitochondrion. These age-induced molecular changes underscore the degenerative aspects of FECD pathogenesis. Although surgical therapies are effective in treating FECD, they all involve tissue transplantation. The research team will now focus on development of novel cytoprotective and anti-aging therapies that could provide alternative and safer treatment options for FECD patients.
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In addition to Dr. Jurkunas, authors on the paper include: Adna Halilovic, Thore Schmedt, Anne-Sophie Benischke, Cecily Hamill, Yuming Chen of Schepens Eye Research Institute of Mass. Eye and Ear and Janine Hertzog Santos, of the National Institutes of Health.
This work was supported by a NEI/NIH RO1 Ey020581, and an Alcon Research Institute Young Investigator Grant.
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. U.S. News & World Report's "Best Hospitals Survey" has consistently ranked the Mass. Eye and Ear Departments of Otolaryngology and Ophthalmology as top in the nation. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.
About Harvard Medical School Department of Ophthalmology
The Harvard Medical School (HMS) Department of Ophthalmology is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at ten HMS affiliate institutions, including Massachusetts Eye and Ear, Schepens Eye Research Institute of 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.
Journal
Antioxidants and Redox Signaling