Similarities Between Humans and Mastiffs Pose New Hope for Observation, Treatment

(Philadelphia, PA) - Night blindness followed by total blindness is the devastating sequence that alters the life of many people who carry a gene defect for the eye disease known as retinitis pigmentosa (RP). Although eye doctors began diagnosing the genetic disease more than a century ago, there is still no cure for RP.

A step toward treatment came recently when researchers at Cornell University's Baker Institute for Animal Health and at the University of Pennsylvania School of Medicine's Scheie Eye Institute discovered that a naturally occurring blindness in the English mastiff dog mimics almost exactly a common form of human RP. Their findings are reported in the April 30th issue of Proceedings of the National Academy of Sciences and today's online PNAS Early Edition.

"The strong similarity between blindness in mastiffs and humans provides us with a much-needed model for treating the disease," said Samuel G. Jacobson MD, PhD, the F.M. Kirby Professor in Penn's Department of Ophthalmology and director of the Center for Hereditary Retinal Degenerations at Scheie. "Years of careful work in the field of veterinary eye genetics by the group at Cornell, led by Drs. Gustavo Aguirre, Gregory Acland and James Kijas, and parallel work with RP patients by our group at Penn were necessary to recognize that the mastiff has a disease that will be important in treatment trials for humans."

According to the researchers, the English mastiff, with an eye approximately as large as a human's and susceptible to a disease that is a near replica of the one in humans, can now serve as a useful model for studying and treating RP.

RP can be caused by many different gene defects. In the every-generation or autosomal dominant form shared by man and mastiff, it is a mutation in the gene that codes for the eye protein rhodopsin that causes RP. Rhodopsin is the light-catching molecule that is at the first stage of vision. Mutations in the rhodopsin gene were linked to RP about 12 years ago. Now, researchers recognize that there are possibly 100 different rhodopsin mutations responsible for causing blindness - the most common form of dominant RP in the U.S.

Jacobson and Penn colleague, Artur V. Cideciyan, PhD, have spent a decade defining the different ways that RP alters the physiology of light sensing cells that harbor the rhodopsin mutations.

"There are essentially two ways in which rhodopsin mutations lead to blindness," commented Cideciyan.

"Some mutations destroy night vision in early life and children are left with only impaired day vision, which then disappears. In other mutations, night vision is present almost throughout life but has a characteristically slowed recovery time in the dark.

Decline of vision occurs but is more gradual and may thus be more amenable to treatment. It is this latter type which is present in the mastiffs."

What does this discovery mean for researchers? Treatments - as simple as supplemental nutrients or as complex as genetic therapy - can now be tested for value and safety.

Members of the Penn team also include Drs. Tomas Aleman and Michael Pianta. Cornell team members also include Drs. Susan Pearce-Kelling and Brian Miller. Sponsors of the research include the F.M. Kirby Foundation, National Eye Institute of the National Institutes of Health, Foundation Fighting Blindness, Macula Vision Research Foundation, and Research to Prevent Blindness.

# # #

The University of Pennsylvania Health System is distinguished not only by its historical significance - first hospital (1751), first medical school (1765), first university teaching hospital (1874), first fully integrated academic health system (1993) - but by its position as a major player on the world stage of medicine in the 21st century. Committed to a three-part mission of education, research, and clinical excellence, UPHS excels in all three areas.


 


 

 

.

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.

Share This Page: