Research targets genes, traits to improve glaucoma screening, prevention, and treatment

"This initiative harnesses resources from the U.S. and India for research that will benefit glaucoma patients around the world," said Belinda Seto, Ph.D., NEI deputy director.

Glaucoma is a group of diseases that damages the eye's optic nerve, the bundle of nerve fibers connecting the eye to the brain. Glaucoma affects about 2.7 million Americans and 60 million people worldwide.

NEI awarded its grant to Massachusetts Eye and Ear (MEE), an affiliate of Harvard Medical School (HMS). DBT has provided funding to the Vision Research Foundation, part of Sankara Nethralaya, a specialty institution in India for ophthalmic care. The combined grants will total more than $1.3 million over three years, pending availability of funds.

Combining research efforts

The primary focus of the research team in India will be on clinical evaluations, collecting samples for genetic testing, and looking for risk factors in patients with glaucoma. The study will include roughly 400 people from 30 families in southern India who share close ancestry.

"We will conduct detailed eye examinations for these large families in India," said Ronnie George, M.D., senior consultant in the Department of Glaucoma at the Vision Research Foundation. The exams include a vision test and quantitative measurements of roughly 40 traits, including ocular pressure, dimensions of the eye and cornea, and size of the optic nerve. "We will also collect blood samples and prepare them for DNA analysis."

Researchers in the U.S. will focus on state-of-the-art genetic analyses to identify risk factors for the clinical traits associated with glaucoma.

"We are planning whole genome sequencing of this unique participant pool," said Janey Wiggs, M.D., Ph.D., associate director of the Ocular Genomics Institute at MEE/HMS. "This study should give us a great opportunity to identify specific genes and gene variants underlying these quantitative traits."

The combined research will build on a pilot study, which was also a collaboration between NEI and DBT, and similar NEI-funded research. The researchers emphasize these projects are excellent examples of how important collaboration and exchange of ideas are for scientific research.

"A unique population combined with cutting-edge technology has the potential to improve our understanding of glaucoma," said George. "It would not be possible for us to do this individually."

PheWAS: a new opportunity to make discoveries

In addition to building a database of gene variants and traits among families with glaucoma, the research team plans to complete a first-ever glaucoma phenome-wide association study (PheWAS).

Wiggs explained that a typical genome-wide association study compares the DNA of a group of people with a particular disease to a group without disease to find the genetic associations. "A PheWAS turns it around where the association of one genetic variant with a variety of different clinical traits is evaluated," she said. Usually researchers need large sample sizes, in the thousands of participants, but the pilot study showed that this type of family-based study can work with smaller sample sizes and still provide meaningful data.

Currently there is no cure for glaucoma, and vision lost from the disease cannot be restored. "The only treatment for glaucoma is to lower intraocular pressure, which is the only modifiable risk factor at the moment," explained Wiggs. "The more we know about the genes that contribute to glaucoma, the better our chances in identifying therapeutic targets."