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Glyn Chidlow, Andreas Ebneter, John P. Wood, Robert Casson; Evidence Supporting An Association Between Expression Of Major Histocompatibility Complex II Expression By Microglia And Optic Nerve Degeneration During Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6576.
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© ARVO (1962-2015); The Authors (2016-present)
Whilst conducting a study investigating the effect of the endotoxin lipopolysaccharide on retinal microglia, we acquired Sprague-Dawley rats from two independent breeding establishments. In a serendipitous finding, we observed that in all of the rats from one of the breeding establishments, the microglial population expressed aberrantly low levels of major histocompatibility complex class II (MHC II). We have previously shown that activated microglia upregulate MHC II expression during optic nerve degeneration induced by ocular hypertension. Since an increasing body of evidence supports the theory that activated microglia contribute to disease progression during glaucoma, and since MHC II expression is a signature event in microglial activation, we hypothesized that optic nerve degeneration during experimental glaucoma would be less severe in the colony of rats with aberrantly low MHC II expression than in the colony with phenotypically normal MHC II expression. The current study tested this hypothesis.
Adult Sprague-Dawley rats from the colony with normal MHC II were designated cohort "NORMAL". Age- and sex-matched adult Sprague-Dawley rats from the colony with the aberrantly low expression of MHC II were designated cohort "LOW". Experimental glaucoma was induced in both cohorts by lasering the trabecular meshwork using a standard protocol. Analysis occurred after 2 weeks of elevated intraocular pressure. Axonal loss was determined by axon counting of transverse sections using targeted sampling. Longitudinal sections were immunohistochemically stained for the following microglial markers: iba1 (total microglial number), ED1 (phagocytic activity), OX6 (MHC II RT1B chain), OX17 (MHC II RT1D chain) and CD74 (MHC II invariant chain). The histological/immunohistochemical outcomes for each group were compared using unpaired, non-parametric statistics.
Peak IOP and IOP exposure were comparable in both experimental groups. The degree of axonal loss following 2 weeks of experimental glaucoma was significantly less in cohort "LOW" compared to cohort "NORMAL". Total microglial number and phagocytic activity as delineated by iba1 and ED1, respectively, reflected the extent of axonal damage in each cohort. As expected, microglial expression of MHC II molecules was substantially lower in the "LOW" cohort compared to the "NORMAL" cohort.
Reduced expression of MHC II by activated microglia in the optic nerve during experimental glaucoma appears to be associated with less severe axonal degeneration. Further studies are needed to elucidate the role of MHC II during experimental glaucoma.
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