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Jin Liu, Sookja Kim Chung, Amy CY Lo; Spatial and temporal analysis of retinal microglia in mouse oxygen-induced retinopathy model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):424.
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The association between retinal microglia and retinopathy of prematurity has been noted and yet unclear. We performed a more detailed quantitative temporal and spatial analysis of retinal microglia in a mouse oxygen-induced retinopathy (OIR) model.
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, P21, P25, and P30, retinal microglia and vessels were visualized by immunostaining 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 retina showed more amoeboid microglia in superficial central (RA: 16.9±7.0 vs. OIR: 44.8±10.4 /mm2) and mid-peripheral (RA: 18.0±2.7 vs. 64.2±16.4 /mm2) areas. On P17, OIR retina showed increased amoeboid (RA: 12.8±4.6 vs. OIR: 148.3±32.8 /mm2) and total (RA: 155.6±11.4 vs. OIR: 213.3±24.9 /mm2), but reduced ramified (RA: 142.8±13.0 vs. OIR: 52.8±15.6 /mm2) microglia in superficial central areas; in superficial mid-peripheral retina, OIR led to an increase in amoeboid (RA: 14.6±2.4 vs. OIR: 189.5±11.1 /mm2) and total (RA: 161.6±16.1 vs. OIR: 276.8±36.0 /mm2) microglia, but a decrease in ramified (RA: 147.0±17.4 vs. OIR: 79.7±31.8 /mm2) microglia in tufts areas; in non-tufts areas, OIR led to increased amoeboid (40.1±22.3 /mm2), ramified (209.0±48.0 /mm2) and total (258.9±38.5 /mm2) microglia; more ramified microglia in deep retina were observed. On P21, more microglia were observed in central (RA: 141.9±8.1 vs. OIR: 340.4±78.5 /mm2) and mid-peripheral (RA: 140.6±18.7 vs. OIR 255.3±91.3 /mm2) superficial retina with more amoeboid form (central: RA: 9.5±5.3 vs. OIR: 263.2±71.4 /mm2; mid-peripheral: RA: 9.1±3.6 vs. OIR: 151.6±79.3 /mm2) in OIR retina. On P25, OIR led to increased microglia in superficial central (RA: 109.1±9.3 vs. OIR: 260.2±20.6 /mm2) and mid-peripheral (RA: 115.3±7.5 vs. OIR: 241.9±20.7 /mm2) retina, as well as in deep retina. Similar patterns were observed on P30.
Retinal microglial activation continues throughout OIR. Activated microglia are associated with vascular abnormalities. The activation of microglia upon OIR challenge last until after the recovery of retinal vessels.
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