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Columbia Researchers Synthesize Compound With Possible Link To MacularDegeneration; Work Is Critical To Pinpointing Causes Of Disease, Scientists Say

form of vitamin A that can absorb a photon of light and, in so doing, change its shape and send a nerve signal to the brain.

Rods and cones shed parts of themselves every day in an ongoing process of renewal. One job performed by RPE cells is to take up and digest this cellular debris. As the RPE cells chew away at the rods and cones, hypothesize the Columbia researchers, they accumulate A2E that has formed from retinal, from digested rhodopsin, and ethanolamine, a component of the cell membrane. The combination of retinal and ethanolamine is precisely what the Columbia chemists mixed to obtain A2E, indicating they may have mimicked the process that takes place in the eye.

One of the questions the researchers have not yet answered is whether A2E forms before or after the RPE takes up cellular debris. Answering that question will help pinpoint how and where the vitamin A derivative is created.

What exactly A2E does to the eye is still a topic of debate. The simple fact of its buildup in RPE cells over time could be all that's needed to impair vision, since the rods and cones depend on RPE cells for a number of functions. But the A2E molecule also has detergent-like properties, and could be poking holes through the surfaces of RPE cells, destroying them. The Columbia scientists also identified a slightly modified structure, or isomer, of A2E, which they named iso-A2E. Previous results from Dr. Dillon's laboratory show that light induces the formation of free radicals from these two pigments. The interconversion of the two forms of A2E could generate free radicals, which could then react with cellular components, rendering them useless.

Researchers in the laboratory of Dr. Sparrow in the Department of Ophthalmology at Columbia are conducting experiments to determine the effects of A2E on RPE cells grown in culture. The researchers also are investigating how A2E is synthesized in the eye, and are planning experiment
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Contact: Bob Nelson
rjn2@columbia.edu
212-854-6580
Columbia University
7-Dec-1998


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