In
a wide variety of retinal degeneration disease
models, the rods and cones die by a special genetically
controlled pathway called apoptosis. This form
of cell death differs from the more classical
form of cell death, termed necrosis because the
dying cells do not attract inflammation nor do
the cells burst and release their cell contents.
Rather, they shrink, fall apart and are removed
by their neighbors. We are interested in this
process because apoptosis of rods in the human
eye, in response to mutations of genes expressed
only in rods seems to spread to the neighboring
cones leading to blindness. Why should cones die
if rods die? Is this invariable or can cones survive
in the absence of rods. Some patients with retinitis
pigmentosa retain excellent vision indicating
that their cones have survived. We now have a
model of this experience in one of our frogs.
The figures show that the rods die as soon as
they begin to express a mutant rab8 protein (rab8-22N).
Thereafter,
the retinal cones survive leading to an all-cone
retina in a frog that is genetically designed
to have a rod-cone retina. These valuable frogs
are being studied to determine what factors
lead to cone survival. Other transgenic frogs
expressing other mutant proteins (mutant
rhodopsins, rab8-67L) appear to develop
a combined slower rod/cone degeneration which
mimics the lesions seen in humans, dogs and
cats. We will study the genetic differences
in these retinas to assess which genes are protective
and which provoke apoptosis.
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Links Plucky Retinal Degeneration Rhodopsin Biosynthesis The Solomon's