Toxic Protein Accumulation and Dry Macular Degeneration
A fair chunk of degenerative aging is caused by the accumulation of various kinds of damaging biochemicals, and here dry macular degeneration is added to that list: "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. ... Concurrent with this discovery, Ambati's laboratory developed two promising therapies for the prevention of the condition. ... 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. 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 or part of the 'dark' genome. The discovery of Alu's toxicity and its control by Dicer should prove of great interest to other researchers in the biological sciences ... Ambati's team developed two potential therapies aimed at preventing geographic atrophy and demonstrated the efficacy of both approaches using laboratory models. The first involves increasing Dicer levels in the retina by 'over-expressing' the enzyme. The second involves blocking Alu RNA using an 'anti-sense' drug that binds and degrades this toxic substance. ... Ambati's group is preparing to start clinical trials by the end of this year."
Link: http://www.eurekalert.org/pub_releases/2011-02/uok-pdi020311.php