Single Cell RNAseq to Characterize Glaucoma Risk Genes
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.
About the Researcher
Dr. Michael Hauser is a geneticist at Duke University. He has studied a wide variety of genetic conditions, including muscular dystrophy, Parkinson disease, post-traumatic stress disorder, and amyotrophic lateral sclerosis; however his primary focus has been on the eye diseases age-related macular degeneration and glaucoma. Most recently, Dr. Hauser has worked with collaborators from Africa and around the world to examine the genetics of glaucoma in people of African ancestry, who are at increased risk of blindness from this disease. Dr. Hauser has used genome-wide association studies involving thousands of affected individuals to identified genetic factors that increase risk of glaucoma. His lab then further explores the mechanism of these risk factors in order to better understand the biology of disease and to pave the way for new treatments and clinical interventions that can benefit patients.
Scientists study the genetics of disease for one reason only--to help improve the diagnosis and treatment of patients. Early in my career I was inspired by meeting Dr. Rand Allingham, a world-renowned clinician and researcher in glaucoma. His passion for treating patients and preventing blindness was infectious, and we became close friends and collaborators as we traveled the world in our studies. We focused our work on the African continent, where the disease is more common and more severe than anywhere else in the world. We have worked with incredibly talented African ophthalmologists, who provide world-class care in extremely challenging situations, and our team has just identified the first African-specific glaucoma risk gene. We lost our friend and colleague Rand Allingham in 2018, but the research team he assembled is dedicated to honoring his legacy by continuing to make great strides in reducing blindness in Africa and around the world. The work supported by the generous donors of the BrightFocus Foundation is critical to understanding how glaucoma risk factors change the biology of the eye and lead to disease. This work will make great strides towards developing new treatments to save our patients’ sight.
First published on: July 3, 2019
Last modified on: November 13, 2019