Dog Discovery a Major Step in Treatment of Genetic Blindness

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.

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