PURPOSE: Retinal microglia (MG) migrate in response to injury, degeneration and inflammation dependent upon both soluble and cognate signals they receive. Previously we found that lipopolysaccharide/interferon-gamma (LPS/IFNgamma) stimulation induces a paradoxical IL-10 mediated suppression of MG migration from retinal explants. Given the high expression of neuronal CD200, which can induce down regulation of CD200 receptor-positive MG activation and neuronal fractalkine expression potentially stimulating MG migration, we wished to further examine their respective roles in the maintenance of MG activation and migration. METHODS: A human retinal explant model of MG migration was used. CD200 receptor and fractalkine receptor stimulation was achieved by addition to explants of CD200:Fc fusion protein and recombinant cytokine respectively, with or without LPS-IFNgamma stimulation that is known to suppress migration. Cell migration and cell activation (iNOS expression) was counted and assessed by numbers of CD45+ cells by immunofluorescence and standardised flow cytometric bead array analysis was performed for cytokine production. RESULTS: Retinal explants expressed fractalkine and CX3CR1 immunohistochemically and by PCR. Addition of Fractalkine and not CD200:Fc induced MG migration from retinal explants. However LPS/IFNgamma-induced suppression of MG migration could only be restored in the presence of CD200:Fc, whilst MG remained iNOS-negative and generated IL-10. CONCLUSIONS: Microglial responses are tightly governed within retina. Although MG do not classically activate following LPS/IFNgamma stimulation, their migration is sustained via CD200R stimulation maintaining their potential to migrate in response to injury.
PURPOSE: Retinal microglia (MG) migrate in response to injury, degeneration and inflammation dependent upon both soluble and cognate signals they receive. Previously we found that lipopolysaccharide/interferon-gamma (LPS/IFNgamma) stimulation induces a paradoxical IL-10 mediated suppression of MG migration from retinal explants. Given the high expression of neuronal CD200, which can induce down regulation of CD200 receptor-positive MG activation and neuronal fractalkine expression potentially stimulating MG migration, we wished to further examine their respective roles in the maintenance of MG activation and migration. METHODS: A human retinal explant model of MG migration was used. CD200 receptor and fractalkine receptor stimulation was achieved by addition to explants of CD200:Fc fusion protein and recombinant cytokine respectively, with or without LPS-IFNgamma stimulation that is known to suppress migration. Cell migration and cell activation (iNOS expression) was counted and assessed by numbers of CD45+ cells by immunofluorescence and standardised flow cytometric bead array analysis was performed for cytokine production. RESULTS: Retinal explants expressed fractalkine and CX3CR1 immunohistochemically and by PCR. Addition of Fractalkine and not CD200:Fc induced MG migration from retinal explants. However LPS/IFNgamma-induced suppression of MG migration could only be restored in the presence of CD200:Fc, whilst MG remained iNOS-negative and generated IL-10. CONCLUSIONS: Microglial responses are tightly governed within retina. Although MG do not classically activate following LPS/IFNgamma stimulation, their migration is sustained via CD200R stimulation maintaining their potential to migrate in response to injury.
Authors: François Willermain; James T Rosenbaum; Bahram Bodaghi; Holly L Rosenzweig; Sarah Childers; Travis Behrend; Gerhild Wildner; Andrew D Dick Journal: Prog Retin Eye Res Date: 2011-11-22 Impact factor: 21.198
Authors: Yongdong Zhou; Kristopher G Sheets; Eric J Knott; Cornelius E Regan; Jingsheng Tuo; Chi-Chao Chan; William C Gordon; Nicolas G Bazan Journal: Exp Eye Res Date: 2011-08-16 Impact factor: 3.467
Authors: Sarah Taylor; Claudia J Calder; Julie Albon; Jonathan T Erichsen; Micheal E Boulton; James E Morgan Journal: Exp Eye Res Date: 2011-02-04 Impact factor: 3.467
Authors: Jingsheng Tuo; Christine M Bojanowski; Min Zhou; Defen Shen; Robert J Ross; Kevin I Rosenberg; D Joshua Cameron; Chunyue Yin; Jeffrey A Kowalak; Zhengping Zhuang; Kang Zhang; Chi-Chao Chan Journal: Invest Ophthalmol Vis Sci Date: 2007-08 Impact factor: 4.799