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Duke Eye Researchers Describe Cascade Of Events That May Lead To Retinal Degeneration

Date:
October 17, 2000
Source:
Duke University Medical Center
Summary:
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.

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.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Duke Eye Researchers Describe Cascade Of Events That May Lead To Retinal Degeneration." ScienceDaily. ScienceDaily, 17 October 2000. <www.sciencedaily.com/releases/2000/10/001017073554.htm>.
Duke University Medical Center. (2000, October 17). Duke Eye Researchers Describe Cascade Of Events That May Lead To Retinal Degeneration. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2000/10/001017073554.htm
Duke University Medical Center. "Duke Eye Researchers Describe Cascade Of Events That May Lead To Retinal Degeneration." ScienceDaily. www.sciencedaily.com/releases/2000/10/001017073554.htm (accessed October 1, 2014).

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