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Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
Published on: May 6, 2015
Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina
Devid Damiani1, John J Alexander, Jason R O'Rourke
1Neuroscience Institute, Italian National Research Council, 56100 Pisa, Italy.
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 of Dicer has been shown to disrupt many developmental processes. In this study, Dicer was removed specifically from the retina using a floxed Dicer conditional allele and the retinal Chx10Cre transgene. Retinal Dicer knock-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 of Dicer resulted in ERG deficits throughout life but not to morphological abnormalities. Northern blot analysis of Dicer-depleted retinas showed a decrease in several miRNAs. The observation that progressive retinal degeneration occurred after removal of Dicer raises the possibility that miRNAs are involved in retinal neurodegenerative disorders.
Insights
Removing Dicer, essential for microRNAs (miRNAs), caused severe retinal degeneration and light response loss in mice. This suggests miRNAs play a crucial role in maintaining retinal health and preventing neurodegeneration.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- MicroRNAs (miRNAs) are key gene regulators.
- Dicer is essential for mature miRNA production and function.
- Dicer removal disrupts developmental processes.
Purpose of the Study:
- To investigate the role of Dicer in retinal development and function.
- To determine the impact of Dicer depletion on retinal cell types and light response.
Main Methods:
- Used a floxed Dicer conditional allele and Chx10Cre transgene to specifically remove Dicer from the retina in mice.
- Analyzed retinal morphology, light response (electroretinogram - ERG), and miRNA levels via Northern blot.
Main Results:
- Retinal Dicer knockout mice showed an inability to respond to light and developed photoreceptor rosettes, cellular disorganization, and widespread degeneration.
- ERG responses (scotopic and photopic) decreased significantly with Dicer depletion.
- Reduced levels of several miRNAs were observed in Dicer-depleted retinas.
- Mice with one Dicer allele removed showed lifelong ERG deficits but no morphological abnormalities.
Conclusions:
- Dicer-dependent miRNAs are critical for maintaining retinal structure and function.
- Progressive retinal degeneration following Dicer removal suggests a role for miRNAs in retinal neurodegenerative disorders.
