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Scientists link another gene to degenerative blindness

Researchers have labored for decades to understand blindness-inducing neurodegenerative diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).

It has been a painstaking scientific journey as AMD and RP each belong to a complex family of disorders, in which every disorder has many forms and each form is encoded with a distinct genetic recipe. Even AMD, a major cause of vision loss in people over 60, is actually a collection of more than 50 diseases.

Now, a team of researchers at the University of Wisconsin-Madison has taken a small but crucial step forward in the ongoing fight against retinal degeneration. Working with fruit flies, the scientists have discovered that a mutation in a common gene called calnexin can derail the light-processing activity of cells and set in motion the gradual breakdown of vision. They report their findings today in the journal Neuron.

Calnexin-found in both fruit flies and humans-functions as a cellular chaperone, ensuring that proteins "fold" or orient properly and get to the parts of the cell they need to go. It also modulates calcium levels, which is critical for proper vision.

When calnexin goes awry, however, calcium levels build up and the proteins that depend on it malfunction, says senior author Nansi Jo Colley, a medical geneticist at the UW-Madison departments of ophthalmology and genetics, and an affiliate of the Eye Research Institute.

At a time when more than 103 genes are known to be involved with AMD and RP, the UW-Madison work could one day help doctors deliver tailor-made treatments to patients who specifically carry calnexin mutations. Because the calnexin protein and other chaperones are also present in the brain, the work can help to answer broader questions about neurodegenerative disease, Colley adds.

"Understanding the basic mechanisms of how proteins are folded holds the key to finding treatments for not only retinal degenerative diseases but also ot
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Contact: Nansi Jo Colley
njcolley@wisc.edu
608-265-5398
University of Wisconsin-Madison
18-Jan-2006


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