Retinal microglia behavior in mouse ocygen-induced retinopathy model: quantitation and distribution

Abstract

Retinopathy of Prematurity(ROP) is a principle cause of childhood blindness worldwide. Retinal microglia are immune cells in the retina, which maintains the homeostasis of local microenvironment. The association between retinal microglia and ROP has been noted but yet unclear. We performed a more detailed analysis on retinal microglia’s quantitative and distributive patterns in a mouse oxygen-induced retinopathy(OIR) model, a well-established rodent model, which mimics ROP. Postnatal day(P) 7 C57BL/6J mouse pups with their nursing mother were exposed to 75% oxygen for 5 days to induce OIR. Room air(RA)-treated pups served as controls. On P12, P17, and P21, retinal microglia and vessels were visualized by immunostaining in whole-mounted retinae under a confocal microscope. Activated(amoeboid) and resting(ramified) microglia in different retinal areas(superficial central/mid-peripheral, deep central/mid-peripheral) were identified, categorized and counted. On P12, OIR retinae showed more amoeboid microglia in superficial central and mid-peripheral areas. On P17, OIR retinae showed increased amoeboid and total, but reduced ramified microglia in superficial central areas; in superficial mid-peripheral retina, OIR led to an increase in amoeboid and total microglia numbers, but a decrease in the number of ramified microglia in tufts areas; in mid-peripheral non-tufts areas, OIR led to increased amoeboid, ramified and total microglia; more ramified microglia were observed in deep OIR retinae. On P21, more microglia were observed in central and mid-peripheral superficial retina with more amoeboid form in OIR retinae. Our observations suggest that(1) retinal microglial activation continues throughout OIR;(2) activated microglia are associated with vascular abnormalities;(3) the activation of microglia persists after full regrowth of retinal vessels in OIR-challenged retina.