New Clues To Hereditary Blinding Disease Found

http://www.healthsentinel.com/news.php?event=news_print_list_item&id=154

"New Clues To Hereditary Blinding Disease Found", Science Daily,
August 24, 2004,
Link: http://www.sciencedaily.com/releases/2004/08/040820083854.htm

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 rhodopsin's 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, taste, smell and many important hormonal
responses in the body.

"Rhodopsin is a prototypical G-protein coupled receptor," said
Aleksandar Stojanovic, a graduate student at DMS who co-authored the
article with Hwa and Jeremiah Stitham at DMS. "The fact that it is so
susceptible to misfolding and breakdown based on the level of zinc
could open new frontiers of research for many diseases."

Hwa and colleagues discovered a cluster of RP mutations localized
within and around the area where zinc is supposed to bind with
rhodopsin. They investigated different amounts of zinc at the
rhodopson binding site to determine what amount leads to a successful
binding and what causes the protein to misfold. According to Hwa, zinc
has a strong presence in the body; the average person has 2.3 grams of
zinc, making it the second most prevalent trace metal behind iron.

"We are slowly figuring out the importance of everyday elements, like
zinc, in maintaining normal function of proteins in the body," said
Hwa. "In addition to rhodopsin, I predict that scientists will find
that more and more proteins and receptors are impacted by trace metals
and may open new areas in the treatment of neurodegenerative and other
types of human diseases."