The Role of DNA Methylation in Ganglion Cell Death

Shannath L Merbs, MD, PhD Johns Hopkins University of Medicine, Wilmer Eye Institute

Co-Principal Investigators

Raymond A. L Enke, PhD Johns Hopkins University


Although glaucoma is a common disease, little has been found in the way of a genetic contribution, suggesting that many genes and environmental factors may act together to cause the disease. In this study, Drs. Merbs, Enke, and colleagues are looking for "epigenetic" changes (modifications to the DNA that can be caused, in part, by the environment) in an animal model of glaucoma. They will also test whether manipulation of DNA methylation (a type of epigenetic change) improves retinal ganglion cell survival.

Project Details

The goal of this study is to begin to define the contribution of non-genetic or "epigenetic" mechanisms causing retinal ganglion cell death in animal models of glaucoma. Drs. Merbs, Enke, and colleagues are comparing epigenetic differences in DNA methylation of the entire genome between healthy ganglion cells and ganglion cells from an animal engineered to have glaucoma. Identified differences will give clues as to what epigenetic changes contribute to the cell death seen in glaucoma. These researchers will then manipulate the DNA methylation in ganglion cells in culture and live animals to see the effects on ganglion cell survival.

While it is known that epigenetic mechanisms contribute to other common diseases such as cancer, very little is known about their contribution to the development and progression of glaucoma. Epigenetic mechanisms are particularly exciting because they represent a way that the environment can interact with one's genes to cause susceptibility to the development of a disease. A better understanding of the contribution of epigenetic mechanisms to glaucoma could lead to totally new treatment strategies.