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An Eyeful of RNA

Editor's Choice in Physiology

By | August 1, 2011

Human retina showing the yellowish "horseshoe-shaped" atrophic region in the center, where the RPE cells have died, revealing the underlying choroid. J. AMBATI, B. GELFAND, AND M. HANSON

The paper

H. Kaneko et al., “DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration,” Nature, 471:325-30, 2011. Free F1000 evaluation

The finding

Millions of people suffer from macular degeneration, an aging-associated disease that slowly destroys central vision. What causes it has long puzzled researchers, but now ophthalmologist Jayakrishna Ambati, at the University of Kentucky, and colleagues have found that sufferers lack an enzyme normally involved in the processing of microRNA, leading to an accumulation of double-stranded RNA and apoptosis in the retina’s pigmented epithelial cells.

The RNA

Three years ago, while studying angiogenesis in the mouse eye, Ambati’s lab found that injecting short, double-helical fragments of RNA prevented new blood vessel growth. They then collected eyes of human patients who had suffered from macular degeneration, and, “to our surprise,” Ambati says, found “huge accumulations of RNA duplexes.”—specifically, double-stranded RNA transcripts of Alu repeats, mobile sequences scattered throughout the genome.

The enzyme

Ambati’s lab tested different RNA-processing enzymes, and found that DICER1, which cuts pre-miRNA into its functional form, was reduced in the eyes of human patients suffering from late-stage macular degeneration. The lack of DICER1 allowed Alu repeats to accumulate, impeding cell function and initiating cell death.

The therapy

Preventing Alu accumulation with antisense drugs “offers hope for some kind of targeted therapy,” according to Orly Reiner of the Weizmann Institute of Science. Ambati has already carried out successful tests in primates, and is planning a clinical trial in a few months.

 

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Comments

Avatar of: Szybalski

Anonymous

August 1, 2011

So we have to construct gene for dicer and perform gene therapy using this dicer gene.      szybalski@oncology.wisc.edu

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Posts: 0

August 1, 2011

So we have to construct gene for dicer and perform gene therapy using this dicer gene.      szybalski@oncology.wisc.edu

Avatar of:

Posts: 0

August 1, 2011

So we have to construct gene for dicer and perform gene therapy using this dicer gene.      szybalski@oncology.wisc.edu

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