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A.–L. Wang, M. Yuan, A.H. Neufeld; Comparison of the Temporal Sequences of Astrocyte and Microglia Activation Following Optic Nerve Injury . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1240.
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© ARVO (1962-2015); The Authors (2016-present)
The anterior optic nerve, the optic nerve head (ONH), contains non–myelinated axons and no oligodendrocytes and, therefore, is a unique structure to study the interactions of two types of glia: astrocytes and microglia. The interactions of these glia during neurodegenerations, such as glaucoma, are largely undefined. We have examined the behaviors and functional markers of microglia and astrocytes in the ONH after optic nerve crush, to assess their role in axonal neurodegeneration.
In 7–8 wks old mice, the left optic nerve was crushed with forceps; the right eye served as the control. At 1, 2, 4, 6 and 10 days after the crush, ONHs were examined by double immunohistochemistry, with antibodies to astrocyte marker, GFAP, and to microglial cell surface marker, GS–IB4. The co–localizations with PCNA (cell division), CCR2 (chemokine receptor), EGFR (differentiation), CD14 (phagocytosis), CD115 (activation), iNOS (cytotoxicity), COX–2 (paracrine cell signaling) and p38 MAPK (signal transduction) were designed to observe the functional changes.
Following optic nerve crush, morphology and functional markers changed significantly both in astrocyte and microglia. At 1 day after crush, astrocyte morphology was not changed but the astrocytes were positive for PCNA, CCR2, EGFR, iNOS and COX–2. These cells remained positive for these markers for at least 6 days after crush. Throughout this period, astrocytes did not express CD14, CD115 or p38 MAPK. Microglia in optic nerve head after crush proliferated (PCNA), migrated (CCR2) and adopted an activated phenotype at day 1 after crush. At 2 days after crush, microglia expressed CD14 (phagocytosis) and CD115 (activation). Four days after crush, microglia maximally expressed most activation markers that were already present at 1–2 days after crush. At 4 days after crush, microglia also expressed p38 MAPK, iNOS and COX–2. At 10 days after crush, microglia decreased in number, lost activation markers and reverted to a quiescent state.
Microglia and astrocytes are activated following optic nerve injury and express different temporal sequences of functional markers.
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