A research team at the University of Iowa has identified the role of key genes and ultraviolet light in a common eye disease.
The disease is called Fuchs endothelial corneal dystrophy (FECD). It causes the loss of corneal endothelial cells, which, left unchecked, leads to vision loss. FECD affects more than 6 million Americans, the authors report. The only treatment to date is surgery.
The researchers explain in the study the process that causes the loss of corneal endothelial cells. In particular, they focused on better understanding and evaluating the role of ferroptosis, a newly identified form of cellular death driven largely by iron concentrations.
The researchers studied samples of corneal endothelial tissue with FECD from 36 patients and compared them with samples from eight patients with healthy corneal endothelial tissue. They found in the FECD samples the presence of certain genes associated with the disease and followed the path by which these genes led to ferroptosis.
They also found through experiments that increases in ultraviolet light created a toxic accumulation of ferrous iron within the corneal cells in the diseased samples.
The researchers then tested different pharmacological compounds known to protect against ferroptosis and other symptoms involved in FECD. They found one drug compound, ubiquinol, helped to prevent corneal cell death.
That means there may be a new way to slow down the progress of FECD or even treat it altogether.
“There is no therapy for FECD despite how common it is, other than surgery,” says Aliasger Salem, the Lyle and Sharon Bighley Endowed Chair and Professor of Pharmaceutical Sciences and Experimental Therapeutics in the College of Pharmacy and the study’s co-corresponding author. “Finding a new way to treat this condition would be a paradigm shift for patients.”
Mark Greiner, professor of Ophthalmology and Visual Sciences in the Carver College of Medicine and a leading FECD surgeon, is a co-corresponding author.
The study is titled “TCF4 trinucleotide repeat expansions and UV irradiation increase susceptibility to ferroptosis in Fuchs endothelial corneal dystrophy.” It was published in the journal Redox Biology.
Study co-authors from Iowa include Sanjib Saha, Jessica Skeie, Christopher Sales, Pornpoj Phruttiwanichakun, Apurva Dusane, Matthew Field, and Chandler Pendleton.
Other co-authors include Gregory Schmidt, Tim Eggleston, and Hanna Shevalye, from the Iowa Lions Eye Bank; Tommy A. Rinkoski, Michael Fautsch, and Keith Baratz from the Mayo Clinic; and Madhuparna Roy and Albert Jun from Johns Hopkins University.
The National Institutes of Health, the Iowa Lions Eye Bank, the UIHC Cornea Research Fund, the M.D. Wagoner & M.A. Greiner Cornea Excellence Fund, the Lyle and Sharon Bighley Chair in Pharmaceutical Sciences, Robert and Joell Brightfelt, and Lloyd and Betty Schermer funded the research.