Genes Linked to Dry AMD -- MEDICA - World Forum for Medicine

Genes Linked to Dry AMD

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People with an activated TLR3 gene
are two to five times more likely to
suffer from permanent vision loss;

The study identifies a functional link between mutation of an immune-system receptor called toll-like receptor 3 (TLR3) and the "dry" type of AMD known as geographic atrophy. The untreatable, progressive disease causes permanent vision loss.

The discovery of the first gene associated specifically with dry AMD opens the door to developing treatments, said Jayakrishna Ambati, a retinal surgeon-scientist in UK's Department of Ophthalmology and Visual Sciences, who along with two others led the multi-institutional collaborative study.

Ambati's lab first discovered a relationship between a dysfunctional TLR3 mutation and decreased ocular cell toxicity in an earlier published study. The current study reports that TLR3 activation leads to death of specific cells in the retina and that people with the normal TLR3 gene are two to five times more likely to develop geographic atrophy than those who carry an inactive TLR3 gene mutation. Ambati's group plans to start clinical trials next year in patients at risk for developing geographic atrophy using new TLR3 inhibitors developed in his lab.

The study may have major preventive and therapeutic implications, according to Hemin Chin, director of the ocular genetics program at the National Eye Institute. "Given its high prevalence in the United States and the world, finding effective prevention and treatment strategies for AMD is of critical importance," Chin said. "This finding represents a major advancement in our understanding of dry AMD, for which effective treatment is not yet available."

Of more immediate significance, an investigational drug modality known as short interfering RNA (siRNA) - currently in advanced phase trials for the "wet" type of AMD - also activates TLR3, as shown by Ambati's earlier study and recently confirmed by another laboratory. Ambati’s new study raises the possibility that siRNA-based therapies could cause geographic atrophy.; Source: University of Kentucky