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Neuron. 2014 Aug 6;83(3):586-600. doi: 10.1016/j.neuron.2014.06.020. Epub 2014 Jul 4.

miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.

Author information

1
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
2
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland.
3
Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Department of Ophthalmology, Eberhard-Karls University, 72076 Tübingen, Germany.
4
Institute for Molecular Health Sciences, ETH, 8093 Zürich.
5
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland. Electronic address: witold.filipowicz@fmi.ch.
6
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Electronic address: botond.roska@fmi.ch.

Abstract

The outer segments of cones serve as light detectors for daylight color vision, and their dysfunction leads to human blindness conditions. We show that the cone-specific disruption of DGCR8 in adult mice led to the loss of miRNAs and the loss of outer segments, resulting in photoreceptors with significantly reduced light responses. However, the number of cones remained unchanged. The loss of the outer segments occurred gradually over 1 month, and during this time the genetic signature of cones decreased. Reexpression of the sensory-cell-specific miR-182 and miR-183 prevented outer segment loss. These miRNAs were also necessary and sufficient for the formation of inner segments, connecting cilia and short outer segments, as well as light responses in stem-cell-derived retinal cultures. Our results show that miR-182- and miR-183-regulated pathways are necessary for cone outer segment maintenance in vivo and functional outer segment formation in vitro.

PMID:
25002228
DOI:
10.1016/j.neuron.2014.06.020
[Indexed for MEDLINE]
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