Abstract
Purpose :
MicroRNAs have been shown to be important regulators of developmental and disease processes. Research in our lab and others has shown that miR-126 is required for proper angiogenesis in several animal models. However, the expression, regulation and function of miR-126 in the mouse choroid vasculature remain unclear. Here we hypothesize that miR-126 is required for choroidal vascular development and/or maintenance.
Methods :
miR-126 knockout mice, miR-126 promoter reporter mice and in vitro models were used to study the expression, regulation and function of miR-126 in choroidal vasculature during development and in adult.
Results :
Our results show that a 5.5 kb EGFL7/miR-126 promoter drives the expression of miR-126 in the choroid endothelial cells (EC) during choroidal vascular development. The expression of miR-126 in the ECs is regulated by flow stress likely through transcription factor Krüppel-like factors. miR-126-/- mice show delayed choroidal vascular development, and adult knockout mice develop focal periphery choroidal vascular atrophy.
Conclusions :
Our study suggests that flow-regulated miR-126 has an important role in modulating mouse choroidal development and maintaining choroidal vasculature integrity. This work may have implications in age-related macular degeneration (AMD), since choroidal circulation is reduced and choroidal capillary degeneration occurs in AMD subjects.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.