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Research Paper|Volume 12, Issue 24|pp 24836—24852

miR-106b suppresses pathological retinal angiogenesis

Catherine Ménard1, Ariel M. Wilson1, Agnieszka Dejda2, Khalil Miloudi3, François Binet2, Sergio Crespo-Garcia2, Célia Parinot2, Frédérique Pilon2, Rachel Juneau2, Elisabeth MMA Andriessen2, Gaëlle Mawambo1, John Paul SanGiovanni4, Vincent De Guire1, Przemyslaw Sapieha1,2,3
  • 1Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal H1T 2M4, Quebec, Canada
  • 2Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal H1T 2M4, Quebec, Canada
  • 3Department of Neurology-Neurosurgery, McGill University, Montreal H3A 2B4, Quebec, Canada
  • 4Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85719, USA
Received: July 4, 2020Accepted: November 13, 2020Published: December 23, 2020
https://doi.org/10.18632/aging.202404

Copyright: © 2020 Ménard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. We recently demonstrated that levels of miR-106b were significantly decreased in the vitreous and plasma of patients with neovascular age-related macular degeneration (AMD). Here we show that expression of the miR-106b-25 cluster is negatively regulated by the unfolded protein response pathway of protein kinase RNA-like ER kinase (PERK) in a mouse model of neovascular AMD. A reduction in levels of miR-106b triggers vascular growth both in vivo and in vitro by inducing production of pro-angiogenic factors. We demonstrate that therapeutic delivery of miR-106b to the retina with lentiviral vectors protects against aberrant retinal angiogenesis in two distinct mouse models of pathological retinal neovascularization. Results from this study suggest that miRNAs such as miR-106b have the potential to be used as multitarget therapeutics for conditions characterized by pathological retinal angiogenesis.