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DURHAM, N.C. - Duke University Medical Center researchers
have shed new light on the process of hereditary retinal
degeneration by demonstrating for the first time how the death
of rod cells in the retina ultimately leads to the demise of
cone cells, another retinal cell type.

Not only do these results help researchers better understand
a disorder that ultimately leads to blindness, but the chain of
events described is an elegant demonstration of how the body
naturally compensates when one of its functions is compromised,
said lead researcher Fulton Wong, research director of the Duke
University Eye Center.

Wong studies retinitis pigmentosa (RP), a broad spectrum of
hereditary eye disorders that typically begin with the early
loss of "night vision," progressing to blindness over many
years. RP is marked by the gradual degeneration of the
specialized photoreceptor cells that line the retina along the
back of the eye. These cells, better known as rods and cones,
translate light that enters the eye into nerve impulses that
travel to the brain for interpretation

"The million dollar question in retinitis pigmentosa has
always been, 'How does a mutation in a rod-specific gene lead
to the death of genetically normal cone cells," Wong said. "We
have shown that the death of rods initiates a chain reaction of
events that ultimately leads to the destruction of cone cells,
and eventually blindness. During this slow process, the neural
network in essence 'rewires' itself to maintain some degree of
sight for some period of time."

The results of the team's study were published Monday in the
November issue of the journal Nature Neuroscience. The
research was funded by the National Institutes of Health, the
Foundation Fighting Blindness and Research to Prevent
Blindness.

So far, researchers have linked more than 30 genes to RP,
which afflicts more than 100,000 Americans. In the typical
course of the disease, which begins in the early years of life,
the rods begin to die in a process known as apoptosis, or
programmed cell death.

As night vision progressively worsens due to the loss of
rods, the cones begin to die as well, which worsens the day
vision. The whole process, which culminates in blindness, can
take many decades to occur, Wong explained.

Since the disease progresses so slowly in humans,
researchers use animal models in which the progression is much
quicker. In his series of experiments, Wong made use of a
special line of transgenic pigs he and Robert Petters at North
Carolina State University created. The team also used a
well-studied mouse model of retinal degeneration and found the
same results.

The pig is an excellent model for studying degenerative
retinal diseases, Wong said, because it has many rods and
cones. Just as importantly, the structure of the pig eye is
very similar to the human eye.

Wong's team focused on the so-called rod bipolar cells,
specialized nerve cells that relay visual information collected
by the rods to the nerves that ultimately carry the visual
impulses back to the brain.

"We found that as the rods die, the rod bipolar cells
connected to them are still intact and want to 'communicate'
with other nerve cells," said You-Wei Peng, assistant research
professor of ophthalmology and neurobiology and first author of
the study. "Since they can no longer communicate with rod
cells, they do the next best thing -- they start to connect to
cone cells."

However, this new connection is a double-edged sword. On one
hand, this new, though incorrect, connection preserves a degree
of sight; on the other, the cone cells receive inappropriate
signals which, over time, lead to their deaths.

"This is an elegant example of nature trying to make the
best out of a bad situation," Wong said. "A new neural
connection is made, and while it is an imperfect connection, it
does allow some degree of sight to continue. In human terms,
these connections bestow an extra decade or so of good, though
progressively worsening, vision."

In broader terms, the finding of how the different types of
nerve cells in the retina interact and respond to each other
has applications throughout the body, Wong said.

"The retina is a part of the central nervous system, in many
ways the most approachable part of the brain," Wong said. "In
any network, it is important to know how the different types of
cells react when one type is damaged or dies. These findings
provide a greater understanding of the cascade of events that
can occur within a neural network."

These findings are also important because they have
implications for current research aimed at treating these
retinal disorders.

"Although there are many different mutations that could
begin the process, our data demonstrate that there is a 'common
downstream' mechanism," Wong said. "Practically, it seems that
these later steps in the disease process might be better
targets for intervention than the individual gene
mutations."

An additional offshoot of the study, Wong added, is that the
pig model he and his colleagues developed has become accepted
by the scientific community as a important new research tool,
which in coming years should make it easier to test potential
new therapies before trying them in humans.