Using a novel high-throughput screening process, scientists have, for the first time, identified molecules with the potential to block the accumulation of a toxic eye protein that can lead to the early onset of glaucoma.
Glaucoma is a group of diseases that can damage the eye’s optic nerve to cause vision loss and blindness. Elevated eye pressure is the main risk factor for optic nerve damage.
Previous research in the field identified a mutant form of a protein called myocilin as a root cause of this increased eye pressure in some patients. Mutant myocilin is toxic to the cells in the part of the eye that regulates pressure. These genetically inherited mutants of myocilin clump together in the front of the eye, preventing proper fluid discharge from the eye, which then raises eye pressure. This cascade of events can lead to early onset glaucoma, which affects several million people before age 35.
To find molecules that bind to mutant myocilin and block its aggregation, researchers designed a simple, high-throughput assay and then screened a library of compounds. They identified two molecules with potential to treat early onset glaucoma.
“These are really the first specific drug targets to treat glaucoma,” said Raquel Lieberman, an associate professor in the Georgia Tech School of Chemistry and Biochemistry. Lieberman presented her findings at the Society for Laboratory Automation and Screening Conference in San Diego, California, and published them in the journal ACS Chemical Biology earlier this year.
The National Institutes of Health and the Pew Scholars Program in the Biomedical Sciences provided support for the research. The work was a collaboration involving Georgia Tech, Emory University, and the University of South Florida.
At the heart of the study was an assay created to take advantage of the fundamental principles of ligand binding.