Research Paper Volume 12, Issue 24 pp 24836—24852
miR-106b suppresses pathological retinal angiogenesis
- 1 Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal H1T 2M4, Quebec, Canada
- 2 Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal H1T 2M4, Quebec, Canada
- 3 Department of Neurology-Neurosurgery, McGill University, Montreal H3A 2B4, Quebec, Canada
- 4 Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85719, USA
Received: July 4, 2020 Accepted: November 13, 2020 Published: December 23, 2020
https://doi.org/10.18632/aging.202404How to Cite
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.