(Philadelphia, PA) - The posthumous gift of eyes from a patient with a rare retinal disease, enhanced S cone syndrome (ESCS), has taught researchers more about the role of NR2E3, the gene that causes this form of blindness. ESCS is an inherited condition that gradually causes night blindness, loss of peripheral vision, and sensitivity to blue light. Researchers at the Scheie Eye Institute at the University of Pennsylvania Medical Center led the study, which was presented in the January 8 edition of the Proceedings of the National Academy of Sciences.

"This is one of those occasions where a generous eye donor has helped scientists to understand a rare disease," said Ann H. Milam, PhD, lead author and a researcher at the F. M. Kirby Center for Molecular Opthalmology within the Scheie Eye Institute. The donated retinas came from a person with two copies of the mutated gene, one from each parent. "Here, we can learn what the NR2E3 gene does by seeing what physically happens when it fails to work correctly."

According to the researchers, NR2E3 has a functional role in the development and arrangement of specialized cells in the retina, called rods and cones, which detect light. While rods allow people to distinguish between dark and light, cones allow people to see colors. There are three types of cones, each named after the wavelength (color) of light they detect - short (blue), medium (green), and long (red), or S, M, and L. To obtain an accurate picture of what color the eyes see, the brain combines information from the three types of cones much as a television similarly combines red, blue, and green light.

"People with ESCS have an overabundance of S cones, which accounts for their sensitivity to blue light," said Milam. "The most common mutation in NR2E3 causes this overabundance of S cones, deficit of rods, L and M cones, and the death of rods and cones in the periphery of the retina."

Researchers still do not have a complete understanding of how rods and cones develop, but their death is a key component to many forms of inherited blindness such as retinitis pigmentosa and age-related macular degeneration. Although ESCS is a rare disease, Milam and her colleagues believe that a better understanding of NR2E3 will lead to a better overall appreciation of the molecular basis of vision.

"One thing is for sure: genes, and the proteins they produce, do not work alone," said Milam. "In untangling the series of events that involve the NR2E3 gene, we will certainly uncover genes involved in both normal and abnormal development of the eye."

Given the relative rarity of ESCS, the researchers are grateful to receive the donated retinas, facilitated by the Foundation Fighting Blindness in Owings Mills, MD. According to Milam, the degree of degeneration in ESCS can vary from patient to patient, which has caused a great deal of confusion in the clinical literature. Indeed, several different diagnoses, from stationary night blindness to reitinitis pigmentosa, have been applied to patients that are now known to have ESCS.

Researchers who collaborated with Milam include doctors S. G. Jacobson, L. Rose, A.Cideciyan, M. Barakat, W. Tang, N Gupta, and T. Aleman of Penn, E. M. Stone and V. C. Sheffield of the University of Iowa, and A. F. Wright of Western General Hospital of Edinburgh, Scotland.

The study was supported in part by Public Health Service research grants, the Foundation Fighting Blindness, the F. M. Kirby Foundation, the Macula Vision Research Foundation, the Macular Disease Foundation, the Fight for Sight research division of Prevent Blindness America, and the Mackall Trust.


# # #

 

.

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 $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 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 $392 million awarded in the 2016 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 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 2016, Penn Medicine provided $393 million to benefit our community.