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Akito Shimouchi, Harumasa Yokota, Chiemi Matsumoto, Taiji Nagaoka, S. Priya Narayanan, Shoji Kimura, Hiroya Kobayashi, Ruth B Caldwell, Akitoshi Yoshida; The morphology of microglia in physiological and pathological retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2263.
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© ARVO (1962-2015); The Authors (2016-present)
Microglial form and function have been shown to be inextricably linked in neurodegenerative conditions. Quantitative analysis of microglial morphology can provide an index of retinal inflammation. This study is the first to quantify microglial shape changes during retinal neovascularization.
Oxygen-induced retinopathy (OIR) was induced by exposing C57BL/6J mice to 75% oxygen from the postnatal day (P)7 to P12 and then returning them to room air until P17. Control mice were kept in room air. Retinal vessels were labeled with lectin and microglia were labeled with Iba1. Confocal images of retinal microglia were prepared and processed with Image J to calculate fractal dimension (DF, structural complexity), form factor (FF, roundness), branching density (BD), convexity (CON) and solidity (SOL, spatial density).
Microglia were uniformly distributed throughout the retinas of control mice on P5, P7and P17. During physiological neovascularization, DF was significantly lower in both central (c) and peripheral (p) retina as compared with the fully vascularized P17 retina. Mean ± SD DF in P5c =1.35±0.02, P5p=1.35±0.10, P7c=1.35±0.05, P7p=1.30±0.06, P17con=1.51±0.31 (p<0.01, n=5). Comparison of the vascularized central retina and avascular peripheral retina at P5 and P7 showed no differences in DF, FF, BD, CON or SOL. Microglia were clustered around neovascular tufts in the P17 OIR retina. Furthermore, DF was significantly lower in both the avascular (1.39±0.06) and neovascular (1.38±0.03) areas of the P17 OIR retina as compared with the P17 control retina (1.51±0.31, p<0.05). Both FF and SOL were significantly higher in areas of neovascularization in P17 OIR retina as compared with the avascular areas (p<0.01). In addition, there was a statistically significant decrease in FF for both P17 OIR and control retinas as compared with the P5 and P7 retinas.
Computer-assisted morphometry demonstrated significant changes in microglial shape during retinal neovascularization. Microglia in areas of pathological neovascularization of the OIR retina showed increased roundness and spatial density as compared with those in the normal retina. Microglial surface irregularity/complexity was reduced during both physiological neovascularization and pathological neovascularization. Studies using adaptive optics and microglia morphometry may offer a biomarker for detecting early retinopathy in patients.
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