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Transport interrupted -- Texas A&M biologists trace cause of early blindness to tissue defect

rafficking defect or if they were dying as a secondary consequence of problems in the RPE," Perkins explains. "Previous research based on studies of human tissue said it was independent of the RPE. We wanted to see if that hypothesis was true. It turns out that it wasnt, but in making the wrong assumption, we found out something even more interestinga different way to cause photoreceptor death."

"If you disrupt protein transport, you kill the cell," Perkins notes. "In this case, the transportation process in the photoreceptors was perfectly normal, but the neighboring RPE was defective, which is why the photoreceptors were dying."

"For this particular disease, we now have the reason why people go blind. If our results translate into treating humans, it should lead to design of potential therapies. But at the very least, it helped settle the controversy of why photoreceptors are failing and why people go blind. Knowing the right cell type to target is half the battle, and were saying its the RPE, not the photoreceptor, and that the functional gene can potentially be added back to the RPE using gene therapy."

In addition to being small, relatively inexpensive and suitable for large-scale genetic experiments, zebrafish make ideal research specimens in Perkins eyes because they are model systems, both for treating human disease and for determining whats important.

"Most people think of mice, monkeys and other furry animals, rather than fish, when they think of research subjects for human diseases," Perkins says. "An advantage of zebrafish is the ability to inexpensively perform forward genetic screens. Using chemicals, we can induce random mutations throughout the genome. We then search through dozens of zebrafish families to identify mutant zebrafish with traits that resemble human diseases. We use the screen to look for specific traits we think are important, but we cant pre-select the gene that caused it."

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Contact: Shana K. Hutchins
shutchins@science.tamu.edu
979-862-1237
Texas A&M University
7-Mar-2007


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