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Publication : Conditional deletion of miR-204 and miR-211 in murine retinal pigment epithelium results in retinal degeneration.

First Author  Du SW Year  2024
Journal  J Biol Chem Volume  300
Issue  6 Pages  107344
PubMed ID  38705389 Mgi Jnum  J:353034
Mgi Id  MGI:7646333 Doi  10.1016/j.jbc.2024.107344
Citation  Du SW, et al. (2024) Conditional deletion of miR-204 and miR-211 in murine retinal pigment epithelium results in retinal degeneration. J Biol Chem 300(6):107344
abstractText  MicroRNAs (miRs) are short, evolutionarily conserved noncoding RNAs that canonically downregulate expression of target genes. The miR family composed of miR-204 and miR-211 is among the most highly expressed miRs in the retinal pigment epithelium (RPE) in both mouse and human and also retains high sequence identity. To assess the role of this miR family in the developed mouse eye, we generated two floxed conditional KO mouse lines crossed to the RPE65-ERT2-Cre driver mouse line to perform an RPE-specific conditional KO of this miR family in adult mice. After Cre-mediated deletion, we observed retinal structural changes by optical coherence tomography; dysfunction and loss of photoreceptors by retinal imaging; and retinal inflammation marked by subretinal infiltration of immune cells by imaging and immunostaining. Single-cell RNA sequencing of diseased RPE and retinas showed potential miR-regulated target genes, as well as changes in noncoding RNAs in the RPE, rod photoreceptors, and Muller glia. This work thus highlights the role of miR-204 and miR-211 in maintaining RPE function and how the loss of miRs in the RPE exerts effects on the neural retina, leading to inflammation and retinal degeneration.
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