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G Tezel, MB Wax; Immunohistochemical Assessment of Glial Mitogen-activated Protein Kinase (MAPK) Activation in Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2182.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether retinal glial cells exhibit a reactivated phenotype in glaucomatous human eyes, and whether the MAPKs are associated with glial reactivation in glaucoma. Methods: The reactivated phenotype of retinal macroglia (astrocytes and Müller cells) and microglia was identified by morphologic assessment and immunostaining for GFAP (a macrogial marker), CD-11b and HLA-DR (microglial markers) in 20 eyes from glaucomatous donors in comparison to 20 control eyes from age-matched normal donors. Retinal expression and localization of the activated forms of MAPKs, including ERK, JNK and p38 kinase, were studied in these eyes using phospho-specific antibodies. In addition, cellular distribution of the activated ERK, JNK and p38 kinase was determined using double immunolabeling techniques. Results: Retinal astrocytes and Müller cells exhibited a hypertrophic morphology and increased expression of GFAP in glaucomatous retinas. Although some alterations were detectable in the number, size and distribution of cells positive for microglial markers in glaucomatous retinas compared to control retinas, the microglial reactivation was not as widespread as macroglial reactivation. Intensity of the immunostaining and the number of labeled cells for activated MAPKs were greater in retina sections from glaucomatous eyes compared to that detected in control eyes, being most prominent for the activated ERK. Double immunolabeling demonstated that the increased retinal immunostaining for ERK was predominantly, but not exclusively, localized to glial cells, whereas the immunostaining for activated JNK or p38 kinase was mainly associated with non-glial cells. Conclusion: These findings provide evidence that retinal glial cells undergo reactivation in glaucomatous human retina. A prominent and persistent activation of ERK in reactivated glial cells suggests that this signaling pathway is likely associated with the induction and/or maintenance of a reactivated glial phenotype in glaucoma. Differential activity of signaling cascades known to be critical for determination of ultimate cell fate, may be associated, in part, with differential susceptibility of neuronal and glial cells to glaucomatous injury.
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