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Pivotal discoveries in age-related macular degeneration
Date:2/6/2011

A team of researchers, led by University of Kentucky ophthalmologist Dr. Jayakrishna Ambati, has discovered a molecular mechanism implicated in geographic atrophy, the major cause of untreatable blindness in the industrialized world.

Their article, "DICER1 Deficit Induces Alu RNA Toxicity in Age-Related Macular Degeneration," was published online by the journal Nature on Feb. 6 (DOI: 10.1038/nature09830).

Concurrent with this discovery, Ambati's laboratory developed two promising therapies for the prevention of the condition. This study also elaborates, for the first time, a disease-causing role for a large section of the human genome once regarded as non-coding "junk DNA."

Geographic atrophy, a condition causing the death of cells in the retina, occurs in the later stages of the "dry type" of macular degeneration, a disease affecting some 10 million older Americans and causing blindness in over 1 million. There is currently no effective treatment for geographic atrophy, as its cause is unknown.

Ambati's team discovered that an accumulation of a toxic type of RNA, called Alu RNA, causes retinal cells to die in patients with geographic atrophy. In a healthy eye, a "Dicer" enzyme degrades the Alu RNA particles.

"We discovered that in patients with geographic atrophy, there is a dramatic reduction of the Dicer enzyme in the retina," said Ambati, professor and vice chair of the Department of Ophthalmology and Visual Sciences and the Dr. E. Vernon and Eloise C. Smith Endowed Chair in Macular Degeneration Research at the UK College of Medicine. "When the levels of Dicer decline, the control system is short-circuited and too much Alu RNA accumulates. This leads to death of the retina."

Alu elements make up a surprisingly large portion about 11 percent by weight of the human genome, comprising more than 1 million sequences. However, their function has been unknown, so they have been called "junk" DNA
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Contact: Keith L. Hautala
keith.hautala@uky.edu
859-257-1754 x231
University of Kentucky
Source:Eurekalert  

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