DICER Enzyme May Play a Critical Role in Stopping Dry AMD
February 24, 2011 - New findings by scientists at the University of Kentucky, led by Dr. Jayakrishna Ambati, may lead to an effective new treatment for dry age-related macular degeneration (AMD).
Dry AMD is the most common cause of vision loss in Canadians over age 50. The disease causes a slow loss of central vision, due to the death of photoreceptors in the central part of the retina (called the macula). In this disease, a layer of retinal cells called the retinal pigment epithelium (RPE) slowly break down, leaving the photoreceptors without support. The breakdown of the RPE is called geographic atrophy.
Dr. Ambati’s team observed that people with geographic atrophy had a build-up of a toxic substance called Alu RNA in their RPE. Alu RNA is produced naturally by the RPE and retina, and in a healthy eye it is broken down by an enzyme called DICER1. The researchers guessed that if the amounts of DICER1 were below normal, Alu RNA could accumulate in the RPE and damage it.
“We’ve discovered that in patients with geographic atrophy, there is a dramatic reduction in the DICER enzyme,” says Dr. Ambati. “When the levels of DICER decline, the control system is short-circuited and too much Alu RNA accumulates. This leads to the death of the retina.” The scientists published their findings in the prestigious journal Nature (online February 6, 2011).
The research team has developed two potential therapies based on their new findings, one aimed at increasing the amount of DICER enzyme, and the other aimed at reducing the production of Alu RNA, in the RPE. Both approaches were successful in laboratory studies, and in principle they should work just as well in human eyes. The team now plans to develop these therapies for testing in humans.
In the video clip below, Dr. Ambati talks about his work on the DICER enzyme and the team’s plan to develop a therapy for dry AMD.