Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye

Jelena Kezic, Heping Xu, Holly R. Chinnery, Connor C. Murphy, Paul G. McMenamin

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    PURPOSE. The chemokine receptor CX3CR1 is expressed by monocyte-derived dendritic cells (DCs) and macrophages. CX3CR1 mediates leukocyte migration and adhesion in homeo-static and inflammatory conditions. Mice lacking Cx3cr1 have altered distribution and function of DC subpopulations in some tissue microenvironments. The present study compares the distribution of monocyte-derived cells in the normal retina and uveal tract as a prelude to the investigation of the role of CX3CR1 in murine models of ocular disease.

    METHODS. Transgenic mice in which either one ( Cx3cr1(gfp/+), heterozygous) or both ( Cx3cr1(gfp/gfp), homozygous) copies of the Cx3cr1 gene have been replaced by the enhanced green fluorescent protein (eGFP) reporter gene were used to investigate the role of Cx3cr1 expression on macrophages and DCs in the normal uveal tract and retina. Chimeric mice were used to investigate turnover of these cells in the normal, uninflamed eye.

    RESULTS. Confocal analysis found no significant differences in the density, phenotype or morphology of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice in immunostained iris, ciliary body, or choroidal and retinal wholemounts. Flow cytometry also failed to detect any difference in the density or cell shape of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice. Chimeras revealed 73% turnover of monocyte-derived cells in the iris and 63% in the choroid by 6 weeks after transplantation.

    CONCLUSIONS. These data illustrate that homing or migration of DCs and macrophages to the uveal tract and retina in normal young mice is not Cx3cr1 dependent and provide a solid foundation for future studies of monocyte-derived cells and the role of Cx3cr1 in models of ocular disease.

    Original languageEnglish
    Pages (from-to)1599-1608
    Number of pages9
    JournalInvestigative Ophthalmology & Visual Science
    Volume49
    Issue number4
    DOIs
    Publication statusPublished - Apr 2008

    Keywords

    • experimental autoimmune uveoretinitis
    • central-nervous-system
    • MHC class-II
    • fractalkine receptor CX(3)CR1
    • macular degeneration
    • ciliary body
    • positive cells
    • leukocyte adhesion
    • immune cells
    • expression

    Cite this

    Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye. / Kezic, Jelena; Xu, Heping; Chinnery, Holly R.; Murphy, Connor C. ; McMenamin, Paul G.

    In: Investigative Ophthalmology & Visual Science, Vol. 49, No. 4, 04.2008, p. 1599-1608.

    Research output: Contribution to journalArticle

    Kezic, Jelena ; Xu, Heping ; Chinnery, Holly R. ; Murphy, Connor C. ; McMenamin, Paul G. / Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye. In: Investigative Ophthalmology & Visual Science. 2008 ; Vol. 49, No. 4. pp. 1599-1608.
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    title = "Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye",
    abstract = "PURPOSE. The chemokine receptor CX3CR1 is expressed by monocyte-derived dendritic cells (DCs) and macrophages. CX3CR1 mediates leukocyte migration and adhesion in homeo-static and inflammatory conditions. Mice lacking Cx3cr1 have altered distribution and function of DC subpopulations in some tissue microenvironments. The present study compares the distribution of monocyte-derived cells in the normal retina and uveal tract as a prelude to the investigation of the role of CX3CR1 in murine models of ocular disease.METHODS. Transgenic mice in which either one ( Cx3cr1(gfp/+), heterozygous) or both ( Cx3cr1(gfp/gfp), homozygous) copies of the Cx3cr1 gene have been replaced by the enhanced green fluorescent protein (eGFP) reporter gene were used to investigate the role of Cx3cr1 expression on macrophages and DCs in the normal uveal tract and retina. Chimeric mice were used to investigate turnover of these cells in the normal, uninflamed eye.RESULTS. Confocal analysis found no significant differences in the density, phenotype or morphology of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice in immunostained iris, ciliary body, or choroidal and retinal wholemounts. Flow cytometry also failed to detect any difference in the density or cell shape of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice. Chimeras revealed 73{\%} turnover of monocyte-derived cells in the iris and 63{\%} in the choroid by 6 weeks after transplantation.CONCLUSIONS. These data illustrate that homing or migration of DCs and macrophages to the uveal tract and retina in normal young mice is not Cx3cr1 dependent and provide a solid foundation for future studies of monocyte-derived cells and the role of Cx3cr1 in models of ocular disease.",
    keywords = "experimental autoimmune uveoretinitis, central-nervous-system, MHC class-II, fractalkine receptor CX(3)CR1, macular degeneration, ciliary body , positive cells, leukocyte adhesion, immune cells, expression",
    author = "Jelena Kezic and Heping Xu and Chinnery, {Holly R.} and Murphy, {Connor C.} and McMenamin, {Paul G.}",
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    TY - JOUR

    T1 - Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye

    AU - Kezic, Jelena

    AU - Xu, Heping

    AU - Chinnery, Holly R.

    AU - Murphy, Connor C.

    AU - McMenamin, Paul G.

    PY - 2008/4

    Y1 - 2008/4

    N2 - PURPOSE. The chemokine receptor CX3CR1 is expressed by monocyte-derived dendritic cells (DCs) and macrophages. CX3CR1 mediates leukocyte migration and adhesion in homeo-static and inflammatory conditions. Mice lacking Cx3cr1 have altered distribution and function of DC subpopulations in some tissue microenvironments. The present study compares the distribution of monocyte-derived cells in the normal retina and uveal tract as a prelude to the investigation of the role of CX3CR1 in murine models of ocular disease.METHODS. Transgenic mice in which either one ( Cx3cr1(gfp/+), heterozygous) or both ( Cx3cr1(gfp/gfp), homozygous) copies of the Cx3cr1 gene have been replaced by the enhanced green fluorescent protein (eGFP) reporter gene were used to investigate the role of Cx3cr1 expression on macrophages and DCs in the normal uveal tract and retina. Chimeric mice were used to investigate turnover of these cells in the normal, uninflamed eye.RESULTS. Confocal analysis found no significant differences in the density, phenotype or morphology of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice in immunostained iris, ciliary body, or choroidal and retinal wholemounts. Flow cytometry also failed to detect any difference in the density or cell shape of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice. Chimeras revealed 73% turnover of monocyte-derived cells in the iris and 63% in the choroid by 6 weeks after transplantation.CONCLUSIONS. These data illustrate that homing or migration of DCs and macrophages to the uveal tract and retina in normal young mice is not Cx3cr1 dependent and provide a solid foundation for future studies of monocyte-derived cells and the role of Cx3cr1 in models of ocular disease.

    AB - PURPOSE. The chemokine receptor CX3CR1 is expressed by monocyte-derived dendritic cells (DCs) and macrophages. CX3CR1 mediates leukocyte migration and adhesion in homeo-static and inflammatory conditions. Mice lacking Cx3cr1 have altered distribution and function of DC subpopulations in some tissue microenvironments. The present study compares the distribution of monocyte-derived cells in the normal retina and uveal tract as a prelude to the investigation of the role of CX3CR1 in murine models of ocular disease.METHODS. Transgenic mice in which either one ( Cx3cr1(gfp/+), heterozygous) or both ( Cx3cr1(gfp/gfp), homozygous) copies of the Cx3cr1 gene have been replaced by the enhanced green fluorescent protein (eGFP) reporter gene were used to investigate the role of Cx3cr1 expression on macrophages and DCs in the normal uveal tract and retina. Chimeric mice were used to investigate turnover of these cells in the normal, uninflamed eye.RESULTS. Confocal analysis found no significant differences in the density, phenotype or morphology of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice in immunostained iris, ciliary body, or choroidal and retinal wholemounts. Flow cytometry also failed to detect any difference in the density or cell shape of eGFP(+) cells between Cx3cr1(gfp/+) and Cx3cr1(gfp/+) mice. Chimeras revealed 73% turnover of monocyte-derived cells in the iris and 63% in the choroid by 6 weeks after transplantation.CONCLUSIONS. These data illustrate that homing or migration of DCs and macrophages to the uveal tract and retina in normal young mice is not Cx3cr1 dependent and provide a solid foundation for future studies of monocyte-derived cells and the role of Cx3cr1 in models of ocular disease.

    KW - experimental autoimmune uveoretinitis

    KW - central-nervous-system

    KW - MHC class-II

    KW - fractalkine receptor CX(3)CR1

    KW - macular degeneration

    KW - ciliary body

    KW - positive cells

    KW - leukocyte adhesion

    KW - immune cells

    KW - expression

    U2 - 10.1167/iovs.07-0953

    DO - 10.1167/iovs.07-0953

    M3 - Article

    VL - 49

    SP - 1599

    EP - 1608

    JO - Investigative Ophthalmology & Visual Science

    JF - Investigative Ophthalmology & Visual Science

    SN - 0146-0404

    IS - 4

    ER -