An international research effort led by scientists from HMS, Massachusetts Eye and Ear, and Case Western Reserve University School of Medicine have identified three genetic associations—TXNRD2, ATXN2, and FOXC1—that influence susceptibility to primary open-angle glaucoma, the most common form of adult-onset glaucoma and the leading cause of irreversible blindness in the world. The findings, published online on January 11, 2016, in Nature Genetics, provide insights that may ultimately be used to develop gene-based testing and treatment strategies for glaucoma.
“Each genetic association tells an interesting story about the disease,” says Janey Wiggs ’85, the Paul Austin Chandler Professor of Ophthalmology at HMS, associate director of the Ocular Genomics Institute at Mass. Eye and Ear, and principal investigator on the study.
TXNRD2 produces a mitochondrial protein that regulates the production of reactive oxygen species in cells. When levels of protein are low, these oxygen species can accumulate and kill the mitochondria. The researchers found that reduced levels of the mitochondrial protein is linked with primary open-angle glaucoma.
It was previously known that a nucleotide repeat in ATXN2 increases the risk of various neurodegenerative diseases, but the scientists also found that gene variants in the repeat regions are linked with primary open-angle glaucoma, suggesting a relationship between neurodegenerative conditions and this form of glaucoma.
Mutations to the protein produced by FOXC1 are known to cause an early-onset type of glaucoma. The researchers found that genetic variations in a region needed for regulating gene expression is associated with primary open-angle glaucoma, indicating that moderate changes in gene expression influence risk of later-onset disease.
Glaucoma is characterized by a rise in eye pressure that can lead to irreparable damage of the optic nerve, which connects the eye to the brain. In advanced stages of the disease, patients become completely blind. Current treatment for the condition is limited to preventing permanent damage to the optic nerve.
“These studies are beginning to define the molecular events that underlie disease risk, and this is the first step toward gene-based diagnostics and therapies,” says Wiggs.
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