March 10, 2006

Gene may increase risk for early glaucoma

ANN ARBOR, MI - A gene that is pivotal to development of the eye may also lead to glaucoma in infants and young people. As scientist Philip J. Gage, Ph.D., learns more about the role of the gene, he believes that “developmental” or early-occurring glaucoma will yield clues to mechanisms at work in more common and widespread forms of the disease.

Glaucoma affects about 3 million people in the U.S., generally those over 40 years of age. If left untreated, the disease can cause permanent vision loss. There are many forms of glaucoma, but all involve damage to the optic nerve, the conduit that carries signals to the brain.

Dr. Gage explains that the gene Pitx2 regulates eye development, instructing embryonic cells to begin forming fundamental structures of the eye. In the November 15 issue of Human Molecular Genetics, he reports that the gene must be present for the proper formation of several structures, including the optic nerve and ocular blood vessels. Using mouse models, he demonstrates how gene mutations could trigger disease.

The study is significant, explains Dr. Gage, because it proposes new mechanisms by which early-onset glaucoma can occur. “Patients with mutations in Pitx2 may have other developmental eye defects that put them at a high risk for glaucoma,” he says. “For example, they could have subtle defects that render the optic nerve susceptible to damage.”

Because there are many forms of glaucoma, it is difficult to point to a precise cause. “Elevated eye pressure occurs in many but not all forms of the disease,” explains Dr. Gage. “At the molecular level, we are beginning to suspect that factors like elevated pressure may have an indirect effect, exerting some kind of force on ‘weak links’ in the eye, such as the defects we found in our study.”

Dr. Gage and graduate student and coauthor Amanda L. Evans are beginning the next phase of research: exploring how Pitx2 regulates other genes and their biochemical pathways. They will continue to search for the mechanistic similarities among types of glaucoma; and they hope, eventually, to identify genes that can be targeted for treatment.

Reprinted from Advances in Research, Spring 2006

Last Modified: Wednesday, 08-Feb-2012 10:23:26 EST