Macular degeneration breakthrough a step closer

Macular degeneration breakthrough a step closer

A major breakthrough has been made in the fights against age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world.

University of Kentucky researchers have made an exciting finding in the "dry" form of AMD as geographic atrophy, which is an untreatable condition that causes blindness in millions of people due to death of retinal pigmented epithelial cells.

In a study published in the current online issue of the premier journal Proceedings of the National Academy of Sciences, lead researcher Dr Jayakrishna Ambati, professor of physiology, and professor and vice chair of ophthalmology and visual sciences at the university, details the advances the team has made.

Previous research from his 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.

Another paper published in the journal Cell showed 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.

Now, Dr Ambati and colleagues have uncovered evidence that activity of the inflammasome, IL-18, and MyD88, were all increased in human eyes with geographic atrophy.

After exhibiting that that blocking any of these components could prevent retinal degeneration in multiple disease models, the researchers say it could herald a new potential therapy for geographic atrophy, for which there is no approved treatment.

The authors also show that Alu RNA, which increases following DICER1 deficit, activates a family of enzymes known as extracellular-signal-regulated kinases (ERK) 1/2.

These were found to be increased in the RPE of human eyes with GA and shown to be key mediators of RPE cell death, and the experts say the work further defines the mechanisms of cell death in human GA and identifies a new therapeutic target for the dry form of AMD.ADNFCR-1853-ID-801424134-ADNFCR

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