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Lian Zhao, Robert N. Fariss, Wai T. Wong; Macrophage Migration Inhibitory Factor Influences Microglial Morphology And Distribution In The Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1369.
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Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that is constitutively expressed by multiple cells in the retina. The functions attributed to MIF include the regulation of macrophage migration and the mediation of inflammation, but the specific function of MIF in the retina is not understood. We investigated the role of MIF in influencing the organization of the retina in particular in the regulation of the location and distribution of microglia.
Retinal tissue from adult (6 week-old) MIF-deficient mice (MIF-/-) and 129S1/SvImJ wild type (WT) mice were analyzed in vibratome sections and in retinal and sclerochoroidal flatmounts. Immunohistochemical staining for Iba1 (microglia), PNA (cone photoreceptors), phalloidin were performed and imaged using confocal microscopy.
In WT retina, microglia in the inner retina demonstrated a ramified morphology and were distributed a regular horizontal pattern with non-overlapping dendritic arbors. In MIF(-/-) retina, microglia were present at higher densities in the IPL and OPL, and had smaller ramified morphologies. These microglia were also more irregularly distributed with partially overlapping dendritic arbors. Significantly, increased numbers of microglia were found in the subretinal space, a zone normally devoid of microglial cells. In MIF(-/-) retina, clusters of microglia were also found in association with local structural abnormalities. Aggregations of irregularly shaped RPE cells and disrupted cone outer segment structures were found in juxtaposition with microglial accumulations in the outer retina. In the inner retina, microglia were also found in association with disruptions in the structure of the OPL.
MIF plays a role in regulating microglia density and distribution in the mouse retina. The absence of MIF results in aberrant localizations of microglia that are associated with deleterious changes in RPE cells and photoreceptors. MIF(-/-) mice may represent a good model system for understanding the regulation of microglial distribution and physiology, and the contributions that microglia may make to retinal pathologies.
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