Polarization of retinal macrophages and (or) microglial cells and common ocular fundus diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Keran , Li Qiaolin ,  Jiang Qin

The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China;

Corresponding author：

Jiang Qin, Email: 1150864285@qq.com

Keywords：

Macrophages/pathology; Microglia/pathology; Retinal diseases/etiology; Review

DOI：

10.3760/cma.j.issn.1005-1015.2017.04.031

Video：

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Retinal macrophages and (or) microglial cells play important roles in regulating inflammation, angiogenesis and tissue repairing, thus affect the development and prognosis of ischemic retinal disease, ocular immune diseases and ocular tumors. Reversing the polarization imbalance of these cells may provide new therapeutic strategies for ischemic retinal disease and ocular immune diseases. The duality of the polarization direction of these cells is still controversial in the inflammatory reaction and pathological angiogenesis of ischemic retinal disease. Meanwhile, the plasticity and diversity of the function need to be further studied and discussed.

Citation： Li Keran, Li Qiaolin, Jiang Qin. Polarization of retinal macrophages and (or) microglial cells and common ocular fundus diseases. Chinese Journal of Ocular Fundus Diseases, 2017, 33(4): 438-441. doi: 10.3760/cma.j.issn.1005-1015.2017.04.031 Copy

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2.	Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization[J]. Front Biosci, 2008, 13: 453-461.
3.	Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions[J]. Immunity, 2010, 32(5): 593-604. DOI: 10.1016/j.immuni.2010.05.007.
4.	Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization[J]. Trends Immunol, 2004, 25(12): 677-686. DOI: 10.1016/j.it.2004.09.015.
5.	Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J]. Trends Immunol, 2002, 23(11): 549-555.
6.	Biswas SK, Gangi L, Paul S, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation) [J]. Blood, 2006, 107(5): 2112-2122. DOI: 10.1182/blood-2005-01-0428.
7.	Duluc D, Corvaisier M, Blanchard S, et al. Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages[J]. Int J Cancer, 2009, 125(2): 367-373. DOI: 10.1002/ijc.24401.
8.	Chen L, Yang P, Kijlstra A. Distribution, markers, and functions of retinal microglia[J]. Ocul Immunol Inflamm, 2002, 10(1): 27-39.
9.	Diaz-Araya CM, Provis JM, Penfold PL, et al. Development of microglial topography in human retina[J]. J Comp Neurol, 1995, 363(1): 53-68. DOI: 10.1002/cne.903630106.
10.	Karlstetter M, Langmann T. Microglia in the aging retina[J]. Adv Exp Med Biol, 2014, 801: 207-212. DOI: 10.1007/978-1-4614-3209-8_27.
11.	Zhang C, Lam TT, Tso MO. Heterogeneous populations of microglia/macrophages in the retina and their activation after retinal ischemia and reperfusion injury[J]. Exp Eye Res, 2005, 81(6): 700-709. DOI: 10.1016/j.exer.2005.04.008.
12.	Langmann T. Microglia activation in retinal degeneration[J]. J Leukoc Biol, 2007, 81(6): 1345-1351. DOI: 10.1189/jlb.0207114.
13.	Buschini E, Piras A, Nuzzi R, et al. Age related macular degeneration and drusen: neuroinflammation in the retina[J]. Prog Neurobiol, 2011, 95(1): 14-25. DOI: 10.1016/j.pneurobio.2011.05.011.
14.	Kumaramanickavel G. Age-related macular degeneration: genetics and biology[J]. Asia Pac J Ophthalmol (Phila), 2016, 5(4): 229-235. DOI: 10.1097/APO.0000000000000223.
15.	Kauppinen A, Paterno JJ, Blasiak J, et al. Inflammation and its role in age-related macular degeneration[J]. Cell Mol Life Sci, 2016, 73(9): 1765-1786. DOI: 10.1007/s00018-016-2147-8.
16.	Yang Y, Liu F, Tang M, et al. Macrophage polarization in experimental and clinical choroidal neovascularization[J/OL]. Sci Rep, 2016, 6: 30933[2016-08-04]. http://dx.doi.org/10.1038/srep30933. DOI: 10.1038/srep30933.
17.	Liu J, Copland DA, Horie S, et al. Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice[J/OL]. PLoS One, 2013, 8(8): 72935[2013-08-16]. http://dx.plos.org/10.1371/journal.pone.0072935. DOI: 10.1371/journal.pone.0072935.
18.	Sakurai E, Anand A, Ambati BK, et al. Macrophage depletion inhibits experimental choroidal neovascularization[J]. Invest Ophthalmol Vis Sci, 2003, 44(8): 3578-3585.
19.	Ambati J, Anand A, Fernandez S, et al. An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice[J]. Nat Med, 2003, 9(11): 1390-1397. DOI: 10.1038/nm950.
20.	Apte RS, Richter J, Herndon J, et al. Macrophages inhibit neovascularization in a murine model of age-related macular degeneration[J/OL]. PLoS Med, 2006, 3(8): 310[2006-08-15]. http://dx.plos.org/10.1371/journal.pmed.0030310. DOI: 10.1371/journal.pmed.0030310.
21.	Cao X, Shen D, Patel MM, et al. Macrophage polarization in the maculae of age-related macular degeneration: a pilot study[J]. Pathol Int, 2011, 61(9): 528-535. DOI: 10.1111/j.1440-1827.2011.02695.x.
22.	Cuenca N, Fernandez-Sanchez L, Campello L, et al. Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases[J]. Prog Retin Eye Res, 2014, 43: 17-75. DOI: 10.1016/j.preteyeres.2014.07.001.
23.	Kelly J, Ali Khan A, Yin J, et al. Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice[J]. J Clin Invest, 2007, 117(11): 3421-3426. DOI: 10.1172/JCI32430.
24.	Zhou Y, Yoshida S, Kubo Y, et al. Different distributions of M1 and M2 macrophages in a mouse model of laser-induced choroidal neovascularization[J]. Mol Med Rep, 2017, 15(6): 3949-3956. DOI: 10.3892/mmr.2017.6491.
25.	He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar[J]. Am J Pathol, 2013, 182(6): 2407-2417. DOI: 10.1016/j.ajpath.2013.02.032.
26.	Barquet LA. Role of VEGF in diseases of the retina[J]. Arch Soc Esp Oftalmol, 2015, 90 Suppl 1: S3-5. DOI: 10.1016/S0365-6691(15)30002-2.
27.	Rutar M, Provis JM. Role of chemokines in shaping macrophage activity in AMD[J]. Adv Exp Med Biol, 2016, 854: 11-16. DOI: 10.1007/978-3-319-17121-0_2.
28.	Sonoda KH. Association of ocular inflammation and innate immune response[J]. Nippon Ganka Gakkai Zasshi, 2008, 112(3): 279-298.
29.	Ma J, Mehta M, Lam G, et al. Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation[J]. Mol Vis, 2014, 20: 881-893.
30.	Marchetti V, Yanes O, Aguilar E, et al. Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy[J]. Sci Rep, 2011, 1: 76. DOI: 10.1038/srep00076.
31.	Nakagawa Y. Endothelial progenitor cell biology in retinopathy of prematurity[J]. Nippon Ganka Gakkai Zasshi, 2013, 117(11): 893-902.
32.	Nakagawa Y, Masuda H, Ito R, et al. Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the murine oxygen-induced retinopathy model[J]. Invest Ophthalmol Vis Sci, 2011, 52(11): 7835-7841. DOI: 10.1167/iovs.10-5880.
33.	Medina RJ, O’Neill CL, O’Doherty TM, et al. Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin-8[J]. Mol Med, 2011, 17(9-10): 1045-1055. DOI: 10.2119/molmed.2011.00129.
34.	Zhu Y, Tan W, Demetriades AM, et al. Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization[J]. Immunology, 2016, 147(4): 414-428. DOI: 10.1111/imm.12571.
35.	Sen HN, Nussenblatt RB. Sympathetic ophthalmia: what have we learned[J]? Am J Ophthalmol, 2009, 148(5): 632-633. DOI: 10.1016/j.ajo.2009.07.024.
36.	Furusato E, Shen D, Cao X, et al. Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study[J]. Histol Histopathol, 2011, 26(9): 1145-1151. DOI: 10.14670/HH-26.1145.
37.	Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics[J/OL]. Adv Drug Deliv Rev, 2017, 2017: E1[2017-04-25]. https://linkinghub.elsevier.com/retrieve/pii/S0169-409X(17)30045-5. DOI: 10.1016/j.addr.2017.04.010.[published online of ahead of print].
38.	Goswami KK, Ghosh T, Ghosh S, et al. Tumor promoting role of anti-tumor macrophages in tumor microenvironment[J]. Cell Immunol, 2017, 316: 1-10. DOI: 10.1016/j.cellimm.2017.04.005.
39.	Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating prognosis[J]. Indian J Ophthalmol, 2015, 63(2): 93-102. DOI: 10.4103/0301-4738.154367.
40.	Bronkhorst IH, Jager MJ. Uveal melanoma: the inflammatory microenvironment[J]. J Innate Immun, 2012, 4(5-6): 454-462. DOI: 10.1159/000334576.
41.	Ly LV, Baghat A, Versluis M, et al. In aged mice, outgrowth of intraocular melanoma depends on proangiogenic M2-type macrophages[J]. J Immunol, 2010, 185(6): 3481-3488. DOI: 10.4049/jimmunol.0903479.
42.	Kalesnikoff J, Sly LM, Hughes MR, et al. The role of SHIP in cytokine-induced signaling[J].. Rev Physiol Biochem Pharmacol, 2003, 149: 87-103. DOI: 10.1007/s10254-003-0016-y.

1. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age[J]. Immunity, 2005, 23(4): 344-346. DOI: 10.1016/j.immuni.2005.10.001.
2. Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization[J]. Front Biosci, 2008, 13: 453-461.
3. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions[J]. Immunity, 2010, 32(5): 593-604. DOI: 10.1016/j.immuni.2010.05.007.
4. Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization[J]. Trends Immunol, 2004, 25(12): 677-686. DOI: 10.1016/j.it.2004.09.015.
5. Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J]. Trends Immunol, 2002, 23(11): 549-555.
6. Biswas SK, Gangi L, Paul S, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation) [J]. Blood, 2006, 107(5): 2112-2122. DOI: 10.1182/blood-2005-01-0428.
7. Duluc D, Corvaisier M, Blanchard S, et al. Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages[J]. Int J Cancer, 2009, 125(2): 367-373. DOI: 10.1002/ijc.24401.
8. Chen L, Yang P, Kijlstra A. Distribution, markers, and functions of retinal microglia[J]. Ocul Immunol Inflamm, 2002, 10(1): 27-39.
9. Diaz-Araya CM, Provis JM, Penfold PL, et al. Development of microglial topography in human retina[J]. J Comp Neurol, 1995, 363(1): 53-68. DOI: 10.1002/cne.903630106.
10. Karlstetter M, Langmann T. Microglia in the aging retina[J]. Adv Exp Med Biol, 2014, 801: 207-212. DOI: 10.1007/978-1-4614-3209-8_27.
11. Zhang C, Lam TT, Tso MO. Heterogeneous populations of microglia/macrophages in the retina and their activation after retinal ischemia and reperfusion injury[J]. Exp Eye Res, 2005, 81(6): 700-709. DOI: 10.1016/j.exer.2005.04.008.
12. Langmann T. Microglia activation in retinal degeneration[J]. J Leukoc Biol, 2007, 81(6): 1345-1351. DOI: 10.1189/jlb.0207114.
13. Buschini E, Piras A, Nuzzi R, et al. Age related macular degeneration and drusen: neuroinflammation in the retina[J]. Prog Neurobiol, 2011, 95(1): 14-25. DOI: 10.1016/j.pneurobio.2011.05.011.
14. Kumaramanickavel G. Age-related macular degeneration: genetics and biology[J]. Asia Pac J Ophthalmol (Phila), 2016, 5(4): 229-235. DOI: 10.1097/APO.0000000000000223.
15. Kauppinen A, Paterno JJ, Blasiak J, et al. Inflammation and its role in age-related macular degeneration[J]. Cell Mol Life Sci, 2016, 73(9): 1765-1786. DOI: 10.1007/s00018-016-2147-8.
16. Yang Y, Liu F, Tang M, et al. Macrophage polarization in experimental and clinical choroidal neovascularization[J/OL]. Sci Rep, 2016, 6: 30933[2016-08-04]. http://dx.doi.org/10.1038/srep30933. DOI: 10.1038/srep30933.
17. Liu J, Copland DA, Horie S, et al. Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice[J/OL]. PLoS One, 2013, 8(8): 72935[2013-08-16]. http://dx.plos.org/10.1371/journal.pone.0072935. DOI: 10.1371/journal.pone.0072935.
18. Sakurai E, Anand A, Ambati BK, et al. Macrophage depletion inhibits experimental choroidal neovascularization[J]. Invest Ophthalmol Vis Sci, 2003, 44(8): 3578-3585.
19. Ambati J, Anand A, Fernandez S, et al. An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice[J]. Nat Med, 2003, 9(11): 1390-1397. DOI: 10.1038/nm950.
20. Apte RS, Richter J, Herndon J, et al. Macrophages inhibit neovascularization in a murine model of age-related macular degeneration[J/OL]. PLoS Med, 2006, 3(8): 310[2006-08-15]. http://dx.plos.org/10.1371/journal.pmed.0030310. DOI: 10.1371/journal.pmed.0030310.
21. Cao X, Shen D, Patel MM, et al. Macrophage polarization in the maculae of age-related macular degeneration: a pilot study[J]. Pathol Int, 2011, 61(9): 528-535. DOI: 10.1111/j.1440-1827.2011.02695.x.
22. Cuenca N, Fernandez-Sanchez L, Campello L, et al. Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases[J]. Prog Retin Eye Res, 2014, 43: 17-75. DOI: 10.1016/j.preteyeres.2014.07.001.
23. Kelly J, Ali Khan A, Yin J, et al. Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice[J]. J Clin Invest, 2007, 117(11): 3421-3426. DOI: 10.1172/JCI32430.
24. Zhou Y, Yoshida S, Kubo Y, et al. Different distributions of M1 and M2 macrophages in a mouse model of laser-induced choroidal neovascularization[J]. Mol Med Rep, 2017, 15(6): 3949-3956. DOI: 10.3892/mmr.2017.6491.
25. He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar[J]. Am J Pathol, 2013, 182(6): 2407-2417. DOI: 10.1016/j.ajpath.2013.02.032.
26. Barquet LA. Role of VEGF in diseases of the retina[J]. Arch Soc Esp Oftalmol, 2015, 90 Suppl 1: S3-5. DOI: 10.1016/S0365-6691(15)30002-2.
27. Rutar M, Provis JM. Role of chemokines in shaping macrophage activity in AMD[J]. Adv Exp Med Biol, 2016, 854: 11-16. DOI: 10.1007/978-3-319-17121-0_2.
28. Sonoda KH. Association of ocular inflammation and innate immune response[J]. Nippon Ganka Gakkai Zasshi, 2008, 112(3): 279-298.
29. Ma J, Mehta M, Lam G, et al. Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation[J]. Mol Vis, 2014, 20: 881-893.
30. Marchetti V, Yanes O, Aguilar E, et al. Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy[J]. Sci Rep, 2011, 1: 76. DOI: 10.1038/srep00076.
31. Nakagawa Y. Endothelial progenitor cell biology in retinopathy of prematurity[J]. Nippon Ganka Gakkai Zasshi, 2013, 117(11): 893-902.
32. Nakagawa Y, Masuda H, Ito R, et al. Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the murine oxygen-induced retinopathy model[J]. Invest Ophthalmol Vis Sci, 2011, 52(11): 7835-7841. DOI: 10.1167/iovs.10-5880.
33. Medina RJ, O’Neill CL, O’Doherty TM, et al. Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin-8[J]. Mol Med, 2011, 17(9-10): 1045-1055. DOI: 10.2119/molmed.2011.00129.
34. Zhu Y, Tan W, Demetriades AM, et al. Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization[J]. Immunology, 2016, 147(4): 414-428. DOI: 10.1111/imm.12571.
35. Sen HN, Nussenblatt RB. Sympathetic ophthalmia: what have we learned[J]? Am J Ophthalmol, 2009, 148(5): 632-633. DOI: 10.1016/j.ajo.2009.07.024.
36. Furusato E, Shen D, Cao X, et al. Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study[J]. Histol Histopathol, 2011, 26(9): 1145-1151. DOI: 10.14670/HH-26.1145.
37. Ngambenjawong C, Gustafson HH, Pun SH. Progress in tumor-associated macrophage (TAM)-targeted therapeutics[J/OL]. Adv Drug Deliv Rev, 2017, 2017: E1[2017-04-25]. https://linkinghub.elsevier.com/retrieve/pii/S0169-409X(17)30045-5. DOI: 10.1016/j.addr.2017.04.010.[published online of ahead of print].
38. Goswami KK, Ghosh T, Ghosh S, et al. Tumor promoting role of anti-tumor macrophages in tumor microenvironment[J]. Cell Immunol, 2017, 316: 1-10. DOI: 10.1016/j.cellimm.2017.04.005.
39. Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating prognosis[J]. Indian J Ophthalmol, 2015, 63(2): 93-102. DOI: 10.4103/0301-4738.154367.
40. Bronkhorst IH, Jager MJ. Uveal melanoma: the inflammatory microenvironment[J]. J Innate Immun, 2012, 4(5-6): 454-462. DOI: 10.1159/000334576.
41. Ly LV, Baghat A, Versluis M, et al. In aged mice, outgrowth of intraocular melanoma depends on proangiogenic M2-type macrophages[J]. J Immunol, 2010, 185(6): 3481-3488. DOI: 10.4049/jimmunol.0903479.
42. Kalesnikoff J, Sly LM, Hughes MR, et al. The role of SHIP in cytokine-induced signaling[J].. Rev Physiol Biochem Pharmacol, 2003, 149: 87-103. DOI: 10.1007/s10254-003-0016-y.

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Chinese Journal of Ocular Fundus Diseases

Polarization of retinal macrophages and (or) microglial cells and common ocular fundus diseases

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