Molecular discovery could lead to prevention of geographic atrophy

Lexington, KY-A team of researchers has discovered a molecular mechanism implicated in geographic atrophy that may lead to the development of ways to prevent the condition.

The investigators’ article, “DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration,” was published online by the journal Nature on Feb. 6. The 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.”

The team, led by University of Kentucky (UK) ophthalmologist Jayakrishna Ambati, MD, 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 Dr. Ambati, professor and vice chairman of the department of ophthalmology and visual sciences and holder of 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.”

Dr. 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. UK has filed patent applications for both technologies, and Dr. Ambati’s group is preparing to start clinical trials by the end of this year.