Vision Researchers
Solve Rare Inherited Retinal Disorder
Focus on Inherited Eye Diseases & Age-Related Macular
Degeneration
July / August 2002
The posthumous donation of eyes from a patient with an inherited
retinal disease, Enhanced S Cone Syndrome (ESCS) has taught
researchers at Penn Eye Care at the Scheie
Eye Institute more about ESCS and the role of NR2E3,
the gene that causes this form of blindness. More importantly,
this discovery is helping researchers learn more about other
genes linked to inherited eye diseases that are currently
untreatable.
The donated retinas were from a patient with two copies
of the mutated gene, one from each parent. Researchers were
able to learn the effects of the NR2E3 gene by microscopic
study of the donor tissues. ESCS, a member of the retinitis
pigmentosa (RP) family of inherited diseases of the retina,
causes night blindness and increased sensitivity to blue
light. NR2E3 has a functional role in the development and
arrangement of vision cells in the retina.
Normal human retinas
contain precisely ordered photoreceptors (rods and cones)
that function to detect light. While rods allow people to
distinguish between dark and light, cones provide color
vision. There are three types of cones, each named after
the wavelength (color) of light it senses: short (S = blue),
medium (M = green), and long (L = red).
Patients with ESCS have an overabundance of S cones, explaining
their increased sensitivity to blue light. They lack rods,
consistent with their lack of night vision. Researchers do
not have a complete understanding of how rods and cones develop,
but the death of these cells is a key component to many forms
of inherited blindness, including RP and age related macular
degeneration (AMD).
Over 100 different genes and gene mutations cause inherited
retinal degeneration. The family of diseases that cause primary
loss of rod vision and secondary loss of cone function is
termed RP. It affects approximately one in 4,000 Americans,
according to Ann H. Milam, PhD, lead author and researcher
at the F.M. Kirby Center for Molecular Ophthalmology and the
Scheie Eye Institute of the University of Pennsylvania Health
System.
Typically, patients with RP become night blind as teenagers
and begin to lose some of their peripheral visual field as
young adults. In advanced RP, many patients' vision is reduced
to a small central island of tunnel vision with loss of their
peripheral visual field.
The Retinal Degeneration Histopathology Laboratory at the
Scheie Eye Institute has the largest collection of preserved
eyes with RP and AMD in the world. In addition to using the
diseased tissues for their own studies, the laboratory shares
tissues with other researchers. Investigators apply through
the Foundation Fighting Blindness to receive samples of the
tissues for their research. "We have sent tissues to
over 70 different laboratories in Asia, Australia, and Europe,"
adds Milam. These donated tissues allow scientists to correlate
the microscopic pathology in the retina with the patient's
visual defects in life.
Penn Eye Care researchers evaluate the patients' retinas
as to their suitability for various forms of treatment currently
being developed. For example, the retinal stimulator being
developed by investigators at the University of Southern
California will be successful only if a diseased retina
retains ganglion
cells, the neurons that convey information to the brain through
their axons in the optic nerve.
Another form of experimental
therapy involves injection of a viral vector containing a
normal gene into the subretinal space between the retinal
pigment epithelium and the photoreceptors. Penn investigators
who have been leaders in this field include Drs. Jean Bennett,
Albert Maguire, Samuel Jacobson, and colleagues. "We
examine a retina with a specific disease at a known age
and
are able to inform the investigators whether other patients
of that age with the same gene defect are likely to have
remaining
photoreceptors and ganglion cells," explains Milam. "Our
major goal is to lay the foundation for developing effective
treatments for inherited eye diseases."
Although there are specific risk factors for AMD, most experts
believe there is a genetic component. AMD is the leading cause
of severe and irreversible visual impairment in the older
population and a third of Americans over age 70 has some degree
of AMD. Utilizing donated eye tissues and light, electron
and confocal microscopy, scientists in the RD Histopathology
Laboratory evaluate the different stages of AMD to learn more
about the disease mechanisms that cause death of the critical
rods and cones.
The Center for Hereditary Retinal Degeneration at the Scheie
Eye Institute provides diagnostic evaluation and clinical
consultations for patients with inherited forms of retinal
degeneration.
Foundation Fighting Blindness
Since 1987, the Foundation Fighting Blindness has supported
an eye donor registry. Patients with retinitis pigmentosa,
age-related macular degeneration, or normal vision may donate
their eyes for research. These preserved eyes are sent to
the Retinal Degeneration Histopathology Laboratory at the
Scheie Eye Institute, Dr. Ann H. Milam, Director.
For information about becoming an eye donor, contact the
Foundation Fighting Blindness at 1-800-683-5555.
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Referring Physicians: To speak with a Penn physician
or refer a patient, contact PennHealth through the secure online
referral form or by calling
1-800-789-PENN
(7366). |
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