DicerInactivation Leads to Progressive Functional and Structural Degeneration of the Mouse Retina

Open Access
Publisher Website
Google Scholar
Abstract
MicroRNAs (miRNAs) are small, highly conserved molecules that have been shown to regulate the expression of genes by binding to specific target mRNAs. Dicer, an RNase III endonuclease, is essential for the production and function of mature miRNAs, and removal ofDicerhas been shown to disrupt many developmental processes. In this study,Dicerwas removed specifically from the retina using a floxedDicerconditional allele and the retinalChx10Cretransgene. RetinalDicerknock-out mice displayed a reproducible inability to respond to light. In addition, morphological defects were observed with the formation of photoreceptor rosettes at postnatal day 16, which progressed to more general cellular disorganization and widespread degeneration of retinal cell types as the animals aged. This was accompanied by concomitant decrease in both scotopic and photopic electroretinogram (ERG) responses. Interestingly, removing a single allele ofDicerresulted in ERG deficits throughout life but not to morphological abnormalities. Northern blot analysis ofDicer-depleted retinas showed a decrease in several miRNAs. The observation that progressive retinal degeneration occurred after removal ofDicerraises the possibility that miRNAs are involved in retinal neurodegenerative disorders.