Tiny grains of color from the iris can clog the eye’s drainage system, and Yale researchers have found genetic clues that may help explain why those grains come loose in some people. Their study links new genetic differences, including ones near the EPHA7 gene, to pigmentary glaucoma and its related condition, pigment dispersion syndrome.
Glaucoma can damage the optic nerve before a person notices symptoms, which is why doctors sometimes call it the “silent killer of sight.” In pigmentary glaucoma, pigment granules detach from the iris, the colored part of the eye, and block the route that normally drains fluid. As fluid builds up, pressure inside the eye can rise and harm the optic nerve. This form of glaucoma mainly affects younger adults.
Researchers already knew that changes in genes involved in making pigment were associated with pigmentary glaucoma. But anatomy alone does not explain who develops the condition: some people with anatomical features linked to pigment dispersion never get it, while others with normal eye anatomy do. “Anatomy explains part of the disease,” said study leader Mathieu Bakhoum, an assistant professor of ophthalmology and visual science at Yale School of Medicine. “But it doesn’t explain everything about it.”
To look for other clues, Bakhoum and first author Mark Dibbs, a Yale medical student, used data from the All of Us research program, led by the U.S. National Institutes of Health. The program brings together health records and genome data, and has enrolled nearly 750,000 people from different racial and ethnic backgrounds.
The team identified more than 500 participants with pigmentary glaucoma or pigment dispersion syndrome, then compared their genetic data with eye-health information from more than 30,000 healthy individuals. One analysis used DNA microarrays, which check many selected genetic variants at once. It covered nearly 900,000 variants. The researchers also used whole-genome sequencing to search across the full genetic code, examining nearly 13 million variants.
The results included pigment-related gene variants already connected to the disease in earlier research. They also revealed previously unreported variants, including ones near EPHA7. The gene helps control how cells move and attach to neighboring cells. That link points to a possible role for the way iris cells hold together, detach and spread. The study, published in Ophthalmology Glaucoma, does not establish that EPHA7 variants cause the disease, but it offers a new lead on how pigment may enter the eye’s drainage system.
The finding could help researchers build a fuller picture of why pigment dispersion progresses to glaucoma in some people but not others. Bakhoum said the genetic risk factors point to a plausible mechanism involving how cells hold on to their neighbors. Further work will be needed to test that explanation and determine whether it can support better ways to identify or treat the condition. For now, the Yale study adds genetic evidence to a disease whose risks have been only partly explained by eye anatomy.