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
"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.
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