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New clues to hereditary blinding disease found

HANOVER, NH Seeking a cure for an inherited disease that causes blindness in over one million people worldwide, Dartmouth Medical School researchers have discovered a critical role for zinc in retinitis pigmentosa. The amount of zinc, a trace metal naturally absorbed by the body, can determine whether a key protein for vision functions normally or misfolds, they found.

An inability to successfully bind zinc to rhodopsin, a light receptor protein in the eye, can trigger retinitis pigmentosa (RP), a degenerative disease that leaves many patients legally blind by the age of 40. The findings parallel similar progress in harnessing essential trace metals in the body to treat several neurodegenerative diseases including Alzheimer's, Parkinson's and Lou Gehrig's Disease.

The research, appearing as the "Paper of the Week" in the August 20 issue of the Journal of Biological Chemistry (JBC), is the first confirmation that zinc is present and plays a significant role in the normal folding and functions of rhodopsin, and if defective, leads to retinal degeneration.

"We have found if there is not enough zinc in the body or there is a mutation in the zinc binding site, the protein rhodopsin will misfold and break down, triggering cell death, degeneration of the retina and eventually blindness," said John Hwa, MD, PhD, assistant professor of pharmacology and toxicology at Dartmouth Medical School. "What is especially exciting about this new direction in our research is that this characteristic of rhodopsin is very similar to other proteins implicated in many neurodegenerative and human diseases. The fact that a trace metal can have such a critical impact on rhodopsins ability to function properly may point to significant advances for research in other devastating illnesses as well."

The principles of the protein rhodopsin may be extended to its relatives: G-protein coupled receptors that mediate numerous functions in the body including sight,
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Contact: Andy Nordhoff
mednews@dartmouth.edu
603-650-1492
Dartmouth Medical School
18-Aug-2004


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