Non-Genetic or "Epigenetic" Mechanisms and Cell Death in Glaucoma

Shannath L Merbs, MD, PhD
Johns Hopkins University of Medicine, Wilmer Eye Institute (Baltimore, MD, United States)

Co-Principal Investigators

Raymond A. L Enke, PhD
Johns Hopkins University
Year Awarded:
Grant Duration:
July 1, 2012 to June 30, 2014
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern
Shannath L Merbs, MD, PhD

The Role of DNA Methylation in Ganglion Cell Death


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.


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.

About the Researcher

Shannath L. Merbs, MD, Ph.D., is an Associate Professor of Ophthalmology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine in Baltimore, MD. She is a board-certified ophthalmologist and clinician-scientist whose laboratory is studying the role that epigenetics, particularly DNA methylation, plays in retinal development and disease. In animal models, she has demonstrated cell-specific DNA methylation patterns in the retina, as well as alterations in DNA methylation in animal models of retinal degeneration. She is a relatively new researcher in the field of glaucoma and is the principal investigator (PI) of an NIH Roadmap Epigenomics Project, Health and Human Disease R01 grant to characterize differentially methylated regions in affected cell types in cadaver eyes with primary open angle glaucoma (POAG) and age-related macular degeneration (AMD). In addition, she is the PI of an X01 grant for CIDR access to identifying differentially methylated DNA regions in the blood of patients with POAG and AMD. Merbs is excited to explore the role that DNA methylation might play in the death of ganglion cells in animal models as described in her BrightFocus application. She believes that a better understanding of the underlying epigenetic mechanisms contributing to the development and progression of glaucoma may help guide novel treatment strategies.


Welsbie DS, Yang Z, Ge Y, Mitchell KL, Zhou X, Martin SE, Berlinicke CA, Hackler L Jr, Fuller J, Fu J, Cao LH, Han B, Auld D, Xue T, Hirai S, Germain L, Simard-Bisson C, Blouin R, Nguyen JV, Davis CH, Enke RA, Boye SL, Merbs SL, Marsh-Armstrong N, Hauswirth WW, DiAntonio A, Nickells RW, Inglese J, Hanes J, Yau KW, Quigley HA, Zack DJ. Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4045-50. doi: 10.1073/pnas.1211284110. Epub 2013 Feb 19. PubMed Icon Google Scholar Icon

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