When it comes to eye diseases, your practice will handle patients who have glaucoma, cataracts or macular degeneration. Those are the big ones that most people worry about and do what they can to avoid or if they do get one of those eye conditions, preserve as much functional vision as possible.
That isn’t to say that your practice won’t get a patient with a rare eye disease. One such rare eye disease is Fuchs’ endothelial corneal dystrophy (FECD). This disease affects the endothelium, which is the layer of cells that line the back of the cornea. Endothelium cells help to pump excess fluid out of the cornea. As these cells die, fluid builds up, leading to swelling and a cloudy cornea. What makes this disease so troublesome is that the changes in endothelium happen gradually over the years before symptoms present themselves.
Research at the University of Texas Southwestern uncovered the genetic changes that led to the disease. In 2015, the lab of Vinod Mootha, M.D., a professor of ophthalmology, found that in most cases of FECD that present in persons in their 50s and 60s are caused by a section of a repeating section DNA that leads to the toxic buildup of repeat RNA in corneal tissue. A gene known as TCF4 holds a three-nucleotide repeat. The number of times the repeat happens various among people. Those that have more than 40 repeats are at high risk for developing FECD. This cellular mechanism is present in other diseases such as Huntington’s Disease and some forms of amyotrophic lateral sclerosis (ALS).
Mootha along with another researcher, David Corey, Ph.D., a professor of pharmacology and biochemistry at the university, wanted to see how the repeats of the TCF4 gene leads to FECD. They compared corneal tissue from 10 people who had FECD with post-mortem corneal tissue from nine eye bank donors. While looking at the eye bank samples, researchers found six samples that had the genetic predisposition for FECD but no sign of the disease on the cornea.
Researchers were able to find a number of molecular changes in corneas of people with FECD and those changes were also present those who had the gene for FECD. The average age of the FECD patients was 66.5 years old and the average age of those with the genetic predisposition for FECD was 46.8 years old. This suggests that the changes start in the cornea years before it becomes a disease.
These changes were related to fibrosis, which is the thickening and scarring of tissue. The researchers feel that fibrosis molecules are possible drug targets and the levels of the fibrosis-related molecules look different in the blood of patients before they develop FECD. In fact, Corey’s lab has developed a way to treat a three-nucleotide repeat diseases by blocking the repetitive genetic material and they hope to use that approach on FECD.
“Our ultimate goal is to try to slow down or stop the disease process so that patients don’t need corneal transplants,” says Mootha. “Based on the results of this study, we have a much better idea of what’s happening early in the disease process, which lets us better track whether we can reverse those early changes.”