Jayakrishna Ambati, vice chair and professor of the Department of Ophthalmology
at the University of Kentucky, and a team of
researchers, are working with a new molecular mechanism associated with
geographic atrophy and are developing two therapies that could
prevent this condition.
atrophy is considered to be the "dry" form of advanced age-related
macular degeneration. This condition occurs due to atrophy to the retinal
pigment epithelial layer below the retina, which then leads to the loss of
photoreceptors in the central part of the eye. The end result is vision loss.
There is no known cure for this condition, and it is currently affecting 10
million older Americans while causing blindness over 1 million.
molecular mechanism that Ambati and his team found was Alu RNA, which is a
toxic type of RNA that plays a disease-causing role in a large section of the
human genome that has been nicknamed "junk" DNA. These Alu-related
elements make up 11 percent of the human genome, and were considered
"junk" DNA because researchers did not understand their role.
RNA accumulates, it kills retinal cells in patients with geographic
atrophy. A "Dicer" enzyme usually degrades these Alu RNA
particles in a healthy eye. This enzyme is greatly reduced in those with
discovered that in patients with geographic atrophy, there is a dramatic
reduction of the Dicer enzyme in the retina," said Ambati. "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."
same time that Ambati and his team made this discovery, they also developed two
therapies that may prevent geographic atrophy. The first therapy increases
Dicer levels in the retina by "over-expressing the enzyme," and the
second therapy blocks Alu RNA with a drug that clings to the toxic structure
and degrades it. Lab models have proved that both therapies could efficiently
prevent geographic atrophy.
findings provide important new clues on the biological basis of geographic
atrophy and may provide avenues for intervention through preventing toxic
accumulation of abnormal RNA products," said Dr. Paul Sieving, director of
the National Eye Institute, which supports Ambati's laboratory.
University of Kentucky has filed for patents on both therapies, and clinical trials
are expected to begin by the end of this year.
This study was published in Nature.