The Genetics of Glaucoma in Individuals of Caucasian and African Ancestry

Large studies have identified many genes and genetic variants that increase risk of glaucoma, but little is known about the mechanism. The work described in this proposal will examine the levels of these genes in individual cells in the retina, and how genetic variants change those levels. It will provide the basic information that will enable us to understand mechanism, and may lead to the development of new treatments for glaucoma. Importantly, this work will follow up new findings in African Americans, a group that is disproportionately affected by glaucoma.

I am collecting additional information about the genetic variants that increase risk of glaucoma. In Aim 1, I will isolate single cells from the human retina–the part of the eye that contains cells that are affected by glaucoma. I will use a new technology that can record all of the cells types in which each individual gene is active, as well as how much of that gene product is made in each cell. One of the main ways that genes increase risk of glaucoma is by changing just how much gene product is made. In Aim 2, I will look at all of the genetic variants that are present in each person whose eyes are examined. I will then be able to see how these genetic variants change the activity of each gene. Many investigators have done this type of analysis in the past, but it always required the entire retina for a single measurement. The new technology that I am using can do the same thing on a single cell, which provides much more useful information. The information that I collect through this work will tell us much more about the ways that glaucoma risk genes work–precisely which cells contain these active genes, and how genetic variants change their activity. This information can tell us much about the root causes of glaucoma which will greatly benefit the development of new drugs and treatments for glaucoma.

Glaucoma is asymptomatic until vision loss has occurred. The low number of ophthalmologists in Nigeria (1 per million people) means that many individuals only seek treatment once their glaucoma has already caused vision loss. Photos of the back of the eye can be taken by a nurse or other individuals, and the subsequent image analysis can highlight possible glaucoma cases without ANY involvement of an ophthalmologist. In this way, a larger number of individuals could be screened, improving early detection of glaucoma while vision loss can be prevented. This same approach could be applied to any low-resource environment.

Glaucoma in African ancestry individuals has a more aggressive course and different genetics than in other ancestry groups. Our results may reveal new ways to diagnose glaucoma in African Americans and other African ancestry groups