April 23, 2002
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.
# # #
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.
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