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D.A. Carter, A.D. Dick; Maintaining Microglial Potential to Migrate is Dependent upon CD200 Receptor Ligation in Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):747.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose Retinal microglia (MG) migrate in response to injury, degeneration and inflammation, dependent upon signals they receive. Control of MG behaviour is governed by cytokine milieu and MG receptor interaction with retinal-derived fractalkine and neuronal CD200. Given our previous findings that (i) lack of CD200 expression results in MG activation and (ii) LPS/IFNγ stimulation induces IL-10 mediated suppression of migration and activation, we wished to further examine whether it is possible to restore steady state MG function following LPS/IFNγ stimulation and thus their ability to respond to insult. Methods We used our previously reported human retinal explant model of MG migration from donor eyes. 5mm biopsy sections of retina were cultured on the membrane of a cell culture insert for up to 72 hours. The effect of MG CD200Receptor ligation was studied by the addition of CD200fc fusion protein with or without LPS/IFNγ stimulation. Cytokine analysis of culture supernatants was also performed by ELISA and flow cytometry. Results MG migration was maximal at 72 hours, and was suppressed following LPS/IFNγ. Addition of CD200fc alone did not effect MG migration. Addition of CD200Fc (10-200ng/ml) did abrogate LPS/IFNγ induced suppression of MG migration inhibiting IL-10, IL-12p70 and TNFα production, whilst high levels of IL-8 and IL-6 were maintained. Conclusion CD200 suppresses classical activation of retinal MG without inhibiting their migratory capacity in vitro. MG respond hierarchically in that despite MG ability to down-regulate function following LPS/IFNγ stimulation further CD200receptor cross-linking will restore MG potential to migrate and thus potentially respond to sites of injury.
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