Abstract
White blood cells, particularly monocytes and their descendants, macrophages, have been implicated in age-related macular degeneration (AMD) pathology. In this minireview, we describe the current knowledge of monocyte and macrophage involvement in AMD. Chemokine receptors present on these cells such as CCR1, CCR2, and CX3CR1, and their roles in monocyte/macrophage recruitment to sites of injury and inflammation in the context of AMD will be reviewed. Mice models for perturbation of chemokine receptors that recapitulate some of the features of AMD are also described. The body of evidence from human and rodent studies at this point in time suggests that monocyte and macrophages may modulate the course of AMD.
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References
Killingsworth MC, Sarks JP, Sarks SH (1990) Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye (Lond) 4(Pt 4):613–621
Penfold P, Killingsworth M, Sarks S (1984) An ultrastructural study of the role of leucocytes and fibroblasts in the breakdown of Bruch’s membrane. Aust J Ophthalmol 12(1):23–31
Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223(2):69–76
Sarks SH, Van Driel D, Maxwell L, Killingsworth M (1980) Softening of drusen and subretinal neovascularization. Trans Ophthalmol Soc U K 100(3):414–422
Cherepanoff S, McMenamin P, Gillies MC, Kettle E, Sarks SH (2010) Bruch’s membrane and choroidal macrophages in early and advanced age-related macular degeneration. Br J Ophthalmol 94(7):918–925
Espinosa-Heidmann DG, Suner IJ, Hernandez EP, Monroy D, Csaky KG, Cousins SW (2003) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44(8):3586–3592
Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44(8):3578–3585
Caicedo A, Espinosa-Heidmann DG, Pina Y, Hernandez EP, Cousins SW (2005) Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization. Exp Eye Res 81(1):38–47
Shi YY, Wang YS, Zhang ZX, Cai Y, Zhou J, Hou HY et al (2011) Monocyte/macrophages promote vasculogenesis in choroidal neovascularization in mice by stimulating SDF-1 expression in RPE cells. Graefes Arch Clin Exp Ophthalmol 249(11):1667–1679
Apte RS, Richter J, Herndon J, Ferguson TA (2006) Macrophages inhibit neovascularization in a murine model of age-related macular degeneration. PLoS Med 3(8):e310
Tsutsumi C, Sonoda KH, Egashira K, Qiao H, Hisatomi T, Nakao S et al (2003) The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization. J Leukoc Biol 74(1):25–32
Kelly J, Ali Khan A, Yin J, Ferguson TA, Apte RS (2007) Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice. J Clin Invest 117(11):3421–3426
Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M et al (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 67(5):699–704
Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN et al (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116(16):e74–80
Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH et al (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118(5):e16–31
Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1):71–82
Frankenberger M, Sternsdorf T, Pechumer H, Pforte A, Ziegler-Heitbrock HW (1996) Differential cytokine expression in human blood monocyte subpopulations: a polymerase chain reaction analysis. Blood 87(1):373–377
Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686
Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177(10):7303–7311
Cao X, Shen D, Patel MM, Tuo J, Johnson TM, Olsen TW et al (2011) Macrophage polarization in the maculae of age-related macular degeneration: a pilot study. Pathol Int 61(9):528–535
Cousins SW, Espinosa-Heidmann DG, Miller DM, Pereira-Simon S, Hernandez EP, Chien H et al (2012) Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization. PLoS Pathog 8(4):e1002671
Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11(11):762–774
Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL et al (2012) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11(5):867–875
Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F (2010) Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol 11:30
Rosenbaum JT, O’Rourke L, Davies G, Wenger C, David L, Robertson JE (1987) Retinal pigment epithelial cells secrete substances that are chemotactic for monocytes. Curr Eye Res 6(6):793–800
Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW et al (2003) Fractalkine preferentially mediates arrest and migration of CD16 + monocytes. J Exp Med 197(12):1701–1707
Shantsila E, Wrigley B, Tapp L, Apostolakis S, Montoro-Garcia S, Drayson MT et al (2011) Immunophenotypic characterization of human monocyte subsets: possible implications for cardiovascular disease pathophysiology. J Thromb Haemost 9(5):1056–1066
Yang D, Elner SG, Chen X, Field MG, Petty HR, Elner VM (2011) MCP-1-activated monocytes induce apoptosis in human retinal pigment epithelium. Invest Ophthalmol Vis Sci 52(8):6026–6034
Suzuki M, Tsujikawa M, Itabe H, Du ZJ, Xie P, Matsumura N et al (2012) Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. J Cell Sci 125(Pt 10):2407–2415
Kyger M, Worley A, Adamus G (2013) Autoimmune responses against photoreceptor antigens during retinal degeneration and their role in macrophage recruitment into retinas of RCS rats. J Neuroimmunol 254(1–2):91–100
Kramer M, Hasanreisoglu M, Feldman A, Axer-Siegel R, Sonis P, Maharshak I et al (2012) Monocyte chemoattractant protein-1 in the aqueous humour of patients with age-related macular degeneration. Clin Experiment Ophthalmol 40(6):617–625
Jonas JB, Tao Y, Neumaier M, Findeisen P (2012) Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration. Acta Ophthalmol 90(5):e381–388
Chen M, Copland DA, Zhao J, Liu J, Forrester JV, Dick AD et al (2012) Persistent inflammation subverts thrombospondin-1-induced regulation of retinal angiogenesis and is driven by CCR2 ligation. Am J Pathol 180(1):235–245
Rutar M, Natoli R, Provis JM (2012) Small interfering RNA-mediated suppression of Ccl2 in Muller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration. J Neuroinflammation 9:221
Zhang M, Xu G, Liu W, Ni Y, Zhou W (2012) Role of fractalkine/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration. PLoS One 7(4):e35446
Chen M, Luo C, Penalva R, Xu H (2013) Paraquat-induced retinal degeneration is exaggerated in CX3CR1 deficient mice and is associated with increased retinal inflammation. Invest Ophthalmol Vis Sci 54(1):682–690
Mattapallil MJ, Wawrousek EF, Chan CC, Zhao H, Roychoudhury J, Ferguson TA et al (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53(6):2921–2927
Luhmann UF, Lange CA, Robbie S, Munro PM, Cowing JA, Armer HE et al (2012) Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling. PLoS One 7(4):e35551
Luhmann UF, Carvalho LS, Robbie SJ, Cowing JA, Duran Y, Munro PM et al (2013) Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration. Exp Eye Res 107C:80–87
Vessey KA, Greferath U, Jobling AI, Phipps JA, Ho T, Waugh M et al (2012) Ccl2/Cx3cr1 knockout mice have inner retinal dysfunction but are not an accelerated model of AMD. Invest Ophthalmol Vis Sci 53(12):7833–7846
Lederman M, Weiss A, Chowers I (2010) Association of neovascular age-related macular degeneration with specific gene expression patterns in peripheral white blood cells. Invest Ophthalmol Vis Sci 51(1):53–58
Grunin M, Burstyn-Cohen T, Hagbi-Levi S, Peled A, Chowers I (2012) Chemokine receptor expression in peripheral blood monocytes from patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 53(9):5292–5300
Haas P, Aggermann T, Nagl M, Steindl-Kuscher K, Krugluger W, Binder S (2011) Implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration. Am J Ophthalmol 152(3):396–399e1
Singh A, Faber C, Falk M, Nissen MH, Hviid TV, Sorensen TL (2011) Altered expression of CD46 and CD59 on leukocytes in neovascular age-related macular degeneration. Am J Ophthalmol 154(1):193–199e2
Cousins SW, Espinosa-Heidmann DG, Csaky KG (2004) Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization? Arch Ophthalmol 122(7):1013–1018
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Grunin, M., Hagbi-Levi, S., Chowers, I. (2014). The Role of Monocytes and Macrophages in Age-Related Macular Degeneration. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_26
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DOI: https://doi.org/10.1007/978-1-4614-3209-8_26
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