Cause of age-related macular degeneration revealed
Washington: A new study led by an Indian origin scientist has made a major breakthrough in the “dry” form of age-related macular degeneration known as geographic atrophy (GA).
GA is an untreatable condition that causes blindness in millions of individuals due to death of retinal pigmented epithelial cells.
Dr. Jayakrishna Ambati, professor of physiology, and professor and vice chair of ophthalmology and visual sciences at University of Kentucky, is a leader in the field of macular degeneration research.
Previous research from the Ambati laboratory published in the journal Nature showed that in human eyes with geographic atrophy there is a deficiency of the enzyme DICER1, leading to accumulation of toxic Alu RNA molecules in the retinal pigmented epithelium.
Now, his team has found that when these RNAs build up in the eye they trigger activation of an immune complex known as the NLRP3 inflammasome.
In turn, this leads to the production of a molecule known as IL-18, which causes death of retinal pigmented epithelial cells and vision loss by activating a critical protein known as MyD88.
Importantly, Ambati and colleagues found evidence that activity of the inflammasome, IL-18, and MyD88 were all increased in human eyes with GA.
They then showed that blocking any of these components could prevent retinal degeneration in multiple disease models. The researchers are excited that blocking these pathways could herald a new potential therapy for GA, for which there is no approved treatment.
The study was recently published in the online edition of the premier journal Cell.
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