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Nobuharu Asai, Masayoshi Nakatani, Takao Nakamura, Kan Ohtsuki; Microglial Activation and Translocator Protein Expression in a Rat Optic Nerve Crush Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2267.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia are located in central nerve system including retina. In normal conditions, they have a ramified morphology. After injury, microglia are activated and their morphology becomes amoeboid. This study was undertaken to characterize the reaction of microglia during degeneration of the optic nerve and retinal ganglion cells (RGCs).
Optic nerve injury and RGC death were induced by optic nerve crush (ONC) in adult male Brown Norway rats. Retinal thicknesses were monitored using spectral-domain optical coherence tomography. At 1 to 14 days after ONC, the retinas were isolated, and cells positive for Brn-3a (a marker of RGCs) were counted. Microglial morphology was observed by using immunohistochemistry for Iba-1, a marker of microglia. Translocator protein (TSPO) mRNA expression levels were assessed by using semiquantitative PCR.
The thickness of ganglion cell complex (GCC) 400 μm from the optic nerve head (ONH) was 89.6 ± 1.6 mm in naive retinas. The GCC thickness was visibly reduced 14 days after ONC (71.7 ± 0.6 μm). The number of Brn-3a positive RGCs decreased slowly over the 14 days (104% ± 2%, 90% ± 5%, 42% ± 2% and 7% ± 1% relative to the numbers in naive retinas, at 1, 3, 7, and 14 days, respectively). The pattern of microglial staining was altered around part of the ONH 3 days after ONC. This alteration of microglia had spread entirely around the ONH at 7 and 14 days after ONC. TSPO mRNA expression was 50% higher than the naive level at 1 day after ONC, and this high expression continued for at least 7 days.
In an ONC model, microglia were activated before reductions were seen in the GCC thickness and number of RGCs. These results suggest that microglia respond to RGC injury at an early stage. Because microglial activation and up-regulation of TSPO expression continued during the progression of tissue degeneration and RGC death, these events might serve as biomarkers of retinal diseases such as glaucoma.
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