PHILADELPHIA — Researchers at the Scheie Eye Institute, the department of Ophthalmology of the University of Pennsylvania have been awarded a five-year, $11.2 million grant from the National Institutes of Health (NIH) to study the genetic risk factors that make African Americans disproportionately more likely to develop primary open-angle glaucoma (POAG). POAG appears almost ten years earlier and progresses more rapidly in African Americans than among Caucasian individuals, making it the leading cause of irreversible blindness in this population. Approximately two million Americans suffer from this form of glaucoma.

“The goal of our study is to identify the genetic and other risk factors that underlie POAG in order to understand this increased burden of disease in African Americans,” says Joan O’Brien, MD, chair of the department of Ophthalmology in Penn’s Perelman School of Medicine, director of the Scheie Eye Institute, and primary investigator on the study.

POAG is a group of diseases that cause progressive and irreversible retinal ganglion cell damage, optic nerve degeneration, and corresponding visual field loss. Once a sufficient number of nerve cells are damaged, blind spots begin to form in the patient’s peripheral field of vision. Even when medical and surgical management are employed, retinal ganglion cell loss can be progressive and irreversible.

“We aim to understand more about the disease, its causes, and what makes African Americans more prone to developing POAG at a younger age and experiencing its most severe form,” says O’Brien. Surprisingly, researchers today still have a poor understanding of what causes POAG, which hinders early identification and focused treatment of the disease.

“We know that there is a genetic component to the disease, as family history has a strong influence,” says O’Brien. The risk of developing POAG increases tenfold when a parent or sibling has the disease, with even larger increases when an identical twin is affected. “By dissecting the disease into subtypes (called endophenotyping) and understanding the different genetic underpinnings of the disease, we can begin to develop better, more targeted treatment options.”

O’Brien will work with Scheie glaucoma specialists, Eydie Miller-Ellis, MD, Prithvi Sankar, MD, and Meredith Regina, MD, PhD, to conduct a comprehensive genetic analysis of POAG in African Americans, for which researchers at University of California, San Francisco (UCSF), will conduct the genotyping. Their genome-wide analysis will help identify the biological pathways and networks underlying the disease in 12,766 patients: 4,400 with POAG and 8,365 controls. Additional data will be provided by the Kaiser Permanente Research Program on Genes, Environment and Health, which in collaboration with UCSF has created a national resource of genetic and health data from 100,000 volunteers. Further analyses of POAG will be performed in collaboration with Kaiser, UCSF and Stanford University investigators. To date, 2,500 Philadelphia-based patients and controls have been enrolled in the study.

“Our hypothesis is that genetic variants influence the risk of POAG and the traits related to that risk, such as intraocular pressure and corneal and retinal nerve fiber layer thickness. In addition, we believe that demographic and ocular risk factors, and medical co-morbidities also contribute to the increased risk of POAG in African Americans,” says O’Brien.

“Once these genomes are analyzed in this understudied and over-affected population, the data can be used to create a risk model of POAG in African-Americans, and inexpensively re-analyzed to elucidate the genetics of other diseases that disproportionately affect this population.”

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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