Researchers from the University of Virginia School of Medicine have found that damaging DNA builds up in the eyes of patients with geographic atrophy, an untreatable, poorly understood type of age-related macular degeneration that causes blindness.
Based mostly on the discovery, investigators believe that it might be possible to treat the disease with frequent HIV drugs or even safer alternatives.
The harmful DNA, often known as Alu cDNA, was previously discovered to be manufactured in the cytoplasm by UVA’s Jayakrishna Ambati, MD, and his colleagues. The new findings are believed to be the first time toxic Alu cDNA accumulation has been confirmed in patients in any disease.
According to a news release, the findings supply insights into how geographic atrophy progresses over time.
“Even we’ve known that geographic atrophy expands over time, we didn’t know the way or why,” Ambati, of UVA’s Department of Ophthalmology and Center for Advanced Vision Science, said in the release. “Our discovery in human eyes that the levels of toxic Alu cDNA are highest at the vanguard of the geographic atrophy lesion provides strong evidence that it’s responsible for this enlargement over time that leads to vision loss.”
About Age-Related Macular Degeneration
Geographic atrophy is a complicated type of age-related macular degeneration, a potentially blinding disease projected to affect 200 million people around the globe. The disease eventually destroys vital cells in the retina, the light-sensing portion of the eye.
According to the release, Ambati, a top expert in macular degeneration, and his colleagues found that this destruction is caused by the buildup of Alu DNA, which the researchers discovered floating in the cytoplasm of cells. That Alu DNA was being manufactured in cytoplasm got here as a surprise, as DNA is usually considered contained within the cell nucleus.
The investigators noted that as Alu DNA accumulates in the eye, it triggers harmful irritation via a part of the immune system known as the inflammasome. The researchers identified how this happens, discovering a beforehand unknown structural side of Alu that triggers the immune mechanism that leads to the death of the vital retinal cells.
That’s the place HIV drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs might come in. The researchers’ new work in lab mice suggests these medicine or safer derivatives are known as Kamuvudines, could block the harmful irritation and protect against retinal cell death.
“Over the past two decades, dozens of clinical trials for geographic atrophy which have focused different pathways have failed,” Ambati said within the release. “These findings from patient eyes present a powerful impetus for a brand new direction.”
According to Ambati, the findings supply additional assist for conducting medical trials testing the drugs in patients with macular degeneration. A previous study of 4 completely different health insurance databases – encompassing greater than 100 million patients over twenty years – found that individuals taking NRTIs were virtually 40% less likely to develop dry macular degeneration.
“Our findings from human eyes show that these toxic molecules, which activate the inflammasome, are most plentiful exactly in the area of greatest disease activity,” Ambati concluded in the release. “We’re very hopeful that a clinical trial of Kamuvudines will be launched soon in geographic atrophy so that we can probably supply a treatment for this devastating condition.”