With lots of meticulous work and a bit of serendipity, researchers at the Medical Center discovered the process by which mutations in rod photoreceptor-specific genes hinder vision. They published their work last week in the November issue of the journal Nature Neuroscience.
The research team studied retinitis pigmentosa, a specific type of eye disorder characterized by dying rod cells. What the researchers found was that as the rod cells, responsible for low-light and night vision, die off, the neural connections to the human brain undergo a re-arrangement. This "re-wiring" within the retina eventually causes cone cells, responsible for daylight vision, to die too.
The rod and cone-shaped cells, located in the back of the eye and in the retina, detect entering light and transmit this information to the brain through retinal nerve cells. Although both types of cells have separate information links to the brain, the researchers uncovered a distinct relationship between the synaptic connections of the rod and cone cells.
"We've found a cell-to-cell mechanism for how rod cell degeneration can lead to cone cell degeneration," said You-Wei Peng, the study's first author and assistant research professor of ophthamology.
"This is the first direct morphological evidence for a mechanism that relates rod cell [degeneration] to cone cells," said Fulton Wong, associate professor of ophthalmology and the study's senior author.
This mechanism kicks into gear when the eye attempts to repair itself as a result of cell death, caused by genetic mutation. In the process, the synaptic connections of the rod cells transfer to the cone cells.
"Our results demonstrate that the rod bipolar cell dendrites have the capability to make alternative connections, when the preferred contacts are apparently not available. Hence, the rules that govern synaptic partnering between rods and rod bipolar cells and between cones and cone bipolar cells are not absolute," the team wrote in the article.
The researchers also hinted that this ability to re-connect with other types of cells "may provide an adaptive advantage for the survival of the retina."
However, the researchers also acknowledge that this re-wiring within the eye causes some anomalous visual responses and may have serious physiological consequences in the retina-among them the eventual death of the cone cells, and ultimately blindness.
Retinitis pigmentosa currently affects approximately 100,000 Americans, usually beginning in adolescence. Those who are affected initially suffer from increasingly poor night vision, and later experience a narrowing field of vision as well as decreased daylight vision. If given enough time, the process eventually leads to blindness-but Peng pointed out that this may take decades. For the most part, retinitis pigmentosa has no effective treatment.
Peng said this research will allow other scientists to test the validity of their respective theories on eye degeneration. Wong and Peng's research has already disproved some existing models about what takes place during hereditary retinal degeneration. The results of the research will also allow further inquiries into the most appropriate point of intervention for treating the disease.
Working closely with Robert Petters, a professor of animal science and genetics at North Carolina State University, the researchers used a genetically modified pig to exhibit the signs of the disorder.
"A pig's eye has a high percentage of cone cells, like the human eye," explained Wong. These facts, as well as the structural similarity between the pig eye and the human eye, make transgenic pigs better study models than traditional transgenic mice.
Still, researchers also proved the results on mice models to assure that their findings are genuine and not an anomaly caused by using the swine model.
There are no immediate clinical trials planned to follow up this study. Wong and Peng plan to further define molecular events that initiate the "switch of allegiance" of a set of synapses from rod cells to cone cells.
"We don't want to jump into a [clinical] trial prematurely," said Wong.
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