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Geographic Atrophy in AMD

Posted by Ilena Di Toro | Posted on August 16, 2022

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that affects the retina. Those with GA can have good vision if the macula, the center part of the retina responsible for sharp, central vision, isn’t damaged.

While there are ways to assess the how well different therapies are working, visual acuity tests don’t show how much vision has deteriorated. So, researchers at the University of Bonn in Germany, National Eye Institute (NEI) and the University of Utah wanted to look into other ways to assess vision. What they studied was reading performance.

Professor Monika Fleckenstein of the University of Bonn studied the correlation of reading ability with findings of geographic atrophy. The research found that both reading ability and reading speed are important functional tests for clinical therapy studies. As for the influence of the worse-seeing eye during reading, also known as “binocular inhibition”, there was no sign of that happening. That means therapeutic approaches in the future should focus on the better-seeing eye in order to get improvement in visual ability.

Still, how does the damage from AMD start in the first place? Research done at the University of Virginia found that one way vision gets damaged is through harmful DNA, known as Alu cDNA that builds up. Jayakrishna Ambati, MD of the University of Virginia’s Department of Ophthalmology and Center for Advanced Vision Science, and his collaborators found this to be manufactured in the cytoplasm.

Ambati’s lab found that the destruction of the macula is caused by the buildup of Alu cDNA. As this builds up in the eye, it leads to inflammation by way of the immune system called the inflammasome, which leads to the death of retinal cells. Sounds bad, doesn’t it? There is a way to stop this from happening. An HIV drug called nucleoside reverse transcriptase inhibitors, or NRTIs and a derivative known as Kamuvudines have been shown in lab mice to block the harmful inflammation and protect against the death of retinal cells.

Ambati feels that this offers support for conducting clinical trials with these drugs in patients with macular degeneration. In fact, a study of four different insurance databases, which comprised of over 100 million patients, found that those who took NRTIs were 40 percent less likely to develop dry macular degeneration. This finding is especially important since other clinical trials for GA that targeted other pathways have failed.

“Our findings from human eyes show that these toxic molecules, which activate the inflammasome, are most abundant precisely in the area of greatest disease activity,” Ambati said. “We are very hopeful that a clinical trial of Kamuvudines will be launched soon in geographic atrophy so that we can potentially offer a treatment for this devastating condition.”


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