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Minhua Wang, W. Ma, L Zhao, R.N. Fariss, W.T. Wong; Adaptive Muller Cell Responses to Microglial Activation in vitro. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2676.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia and Muller cells in the retina are involved in tissue responses to injury/inflammation that are generally known as "gliosis". We explored this response by examining the effects of activated microglia, the early responders to injury, on Muller cells in vitro.
Primary mouse Muller cells were exposed for 48 hrs in a co-culture system to primary mouse retinal microglia that had been previously activated with LPS. Muller cells cultured alone or cultured with unactivated microglia served as controls. Muller cells post-exposure were analyzed in terms of gene expression by rt-PCR, proliferative activity by BrdU labeling, and apoptosis by TUNEL labeling. Muller cell-conditioned media, collected 24 hrs post-exposure to microglia, were analyzed by ELISA and evaluated for the ability to provide neuroprotection to 661W photoreceptors exposed to H202.
Muller cells co-cultured with activated microglia demonstrated significant changes in morphology compared to controls by becoming more elongated and spindle-shaped. Proliferative activity was also markedly decreased post-exposure, but without an increase in apoptosis. Expression of molecular markers of Muller cell gliosis such as GLAST and vimentin were not increased but were in fact decreased, while levels of GFAP remained very low. Among growth factors, the expression levels of GDNF were increased, with NGF, BDNF, and bFGF remaining relatively unchanged. Expression of proinflammatory cytokines, IL6, IL1b, and CCL2 were increased, as were levels of iNOS, VCAM1, and ICAM1. Conditioned media from Muller cells exposed to activated microglia were also able to provide greater neuroprotection to photoreceptors relative to that from unexposed Muller cells.
Activated microglia were capable of signaling to and influencing Muller cells in vitro. Typical changes associated with gliosis such as cellular hypertrophy, increased intermediate filament expression, and proliferation were however not induced. Instead, exposed Muller cells demonstrated an elongated morphology, decreased proliferation and vimentin expression, and an increased neuroprotective capacity. Muller cells may respond to the early induction of microglial activation following tissue injury by inducing adaptive and protective effects in the retina.
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