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Graefe's Archive for Clinical and Experimental Ophthalmology
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 12/2016

01-12-2016 | Pathology

Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD)

Authors: Zhaojiang Du, Xuemei Wu, Meixia Song, Peng Li, Li Wang

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 12/2016

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Abstract

Purpose

Age-related macular degeneration (AMD) is a major cause of progressive and degenerative visual impairment. Although the exact pathogenic mechanism of AMD is still unknown, clinical observations such as the high accumulation of oxidative products and macrophages in retina suggest the importance of oxidative stress and inflammation in AMD.

Methods

Mouse photoreceptor-derived 661 W cells and human ARPE-19 cells were treated with oxidized phospholipids (Ox-PC) or H2O2 to mimic oxidative damage. The effect of monocyte chemoattractant protein 1 (MCP-1) secreted by retina cells on the migration of monocyte macrophage RAW 264.7 cells was determined using transwell chambers and antibody neutralization assay. MCP-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and vascular endothelial growth factor (VEGF) that secreted into supernatant were measured by ELISA and their intracellular expression was detected by qRT-PCR and western blot. Intracellular Ox-PC level was detected by competitive ELISA. The amount of migrated RAW 264.7 cells was counted by flow cytometry.

Results

Oxidative damage by both H2O2 and Ox-PC induced the secretion of MCP-1 in human ARPE-19 and mouse 661 W cells. MCP-1 induced by oxidative damage enhanced the migration ability of macrophage RAW 264.7 cells and the secretion of TNF-α, IL-1β and VEGF, which could be reduced by anti-MCP-1 neutralizing antibodies.

Conclusion

The results indicated that oxidative damage increases intracellular Ox-PC and the secretion of MCP-1 in retina cells. The increased MCP-1 induced by oxidative damage attracts macrophages to retinas, and macrophages release pro-inflammatory factor and promote the process of AMD.
Literature
1.
Rakoczy EP, Lai CM, Constable IJ (2015) Neovascular age-related macular degeneration: secretion gene therapy. In: Gene-and cell-based treatment strategies for the eye. Springer, Berlin
2.
Pascolini D, Mariotti SP (2012) Global estimates of visual impairment: 2010. Br J Ophthalmol 96:614–618CrossRefPubMed
3.
Hageman GS, Luthert PJ, Chong NV, Johnson LV, Anderson DH, Mullins RF (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 20:705–732CrossRefPubMed
4.
Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A (2014) Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet 15:151–171CrossRefPubMedPubMedCentral
5.
van Lookeren Campagne M, LeCouter J, Yaspan BL, Ye W (2014) Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol 232:151–164CrossRefPubMed
6.
Swaroop A, Chew EY, Rickman CB, Abecasis GR (2009) Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet 10:19–43CrossRefPubMedPubMedCentral
7.
Kanda A, Abecasis G, Swaroop A (2008) Inflammation in the pathogenesis of age-related macular degeneration. Br J Ophthalmol 92:448–450CrossRefPubMed
8.
9.
Hammond BR, Wooten BR, Snodderly DM (1996) Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Vis Res 36:3003–3009CrossRefPubMed
10.
Khan J, Thurlby D, Shahid H, Clayton D, Yates J, Bradley M, Moore A, Bird A (2006) Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation. Br J Ophthalmol 90:75–80CrossRefPubMedPubMedCentral
11.
van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de Jong PT (2005) Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 294:3101–3107CrossRefPubMed
12.
Beatty S, Koh H-H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115–134CrossRefPubMed
13.
Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A 99:14682–14687CrossRefPubMedPubMedCentral
14.
Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL, Salomon RG, Perez VL (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14:194–198CrossRefPubMedPubMedCentral
15.
Liu SX, Hou FF, Guo ZJ, Nagai R, Zhang WR, Liu ZQ, Zhou ZM, Zhou M, Xie D, Wang GB (2006) Advanced oxidation protein products accelerate atherosclerosis through promoting oxidative stress and inflammation. Arterioscler Thromb Vasc Biol 26:1156–1162CrossRefPubMed
16.
17.
Tanaka T, Terada M, Ariyoshi K, Morimoto K (2010) Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation. Biochem Biophys Res Commun 399:677–682CrossRefPubMed
18.
19.
Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interf Cytokine Res 29:313–326CrossRef
20.
Jonas JB, Tao Y, Neumaier M, Findeisen P (2010) Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration. Arch Ophthalmol 128:1281–1286CrossRefPubMed
21.
Itabe H, Takeshima E, Iwasaki H, Kimura J, Yoshida Y, Imanaka T, Takano T (1994) A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. J Biol Chem 269:15274–15279PubMed
22.
Suzuki M, Tsujikawa M, Itabe H, Du ZJ, Xie P, Matsumura N, Fu X, Zhang R, Sonoda KH, Egashira K (2012) Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration. J Cell Sci 125:2407–2415CrossRefPubMedPubMedCentral
23.
Wakamatsu TH, Dogru M, Tsubota K (2008) Tearful relations: oxidative stress, inflammation and eye diseases. Arq Bras Oftalmol 71:72–79CrossRefPubMed
24.
Lee S, Birukov KG, Romanoski CE, Springstead JR, Lusis AJ, Berliner JA (2012) Role of phospholipid oxidation products in atherosclerosis. Circ Res 111:778–799CrossRefPubMedPubMedCentral
25.
Suzuki M, Kamei M, Itabe H, Yoneda K, Bando H, Kume N, Tano Y (2007) Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration. Mol Vis 13:772–778PubMedPubMedCentral
26.
Melgarejo E, Medina MÁ, Sánchez-Jiménez F, Urdiales JL (2009) Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. Int J Biochem Cell Biol 41:998–1001CrossRefPubMed
27.
Armaiz-Pena GN, Gonzalez-Villasana V, Nagaraja AS, Rodriguez-Aguayo C, Sadaoui NC, Stone RL, Matsuo K, Dalton HJ, Previs RA, Jennings NB (2015) Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth. Oncotarget 6:4266–4273CrossRefPubMed
28.
Austin BA, Liu B, Li Z, Nussenblatt RB (2009) Biologically active fibronectin fragments stimulate release of MCP-1 and catabolic cytokines from murine retinal pigment epithelium. Invest Ophthalmol Vis Sci 50:2896–2902CrossRefPubMedPubMedCentral
29.
O’Hayre M, Salanga C, Handel T, Allen S (2008) Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochem J 409:635–649CrossRefPubMed
30.
Niu J, Azfer A, Zhelyabovska O, Fatma S, Kolattukudy PE (2008) Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP). J Biol Chem 283:14542–14551CrossRefPubMedPubMedCentral
31.
Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-β and TNF-α, by human macrophages. J Immunol 160:3513–3521PubMed
32.
33.
Duvall J, Tso MO (1985) Cellular mechanisms of resolution of drusen after laser coagulation: an experimental study. Arch Ophthalmol 103:694–703CrossRefPubMed
34.
Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati BK (2003) An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice. Nat Med 9:1390–1397CrossRefPubMed
35.
Sola-Villa D, Camacho M, Sola R, Soler M, Diaz J, Vila L (2006) IL-1β induces VEGF, independently of PGE2 induction, mainly through the PI3-K/mTOR pathway in renal mesangial cells. Kidney Int 70:1935–1941CrossRefPubMed
36.
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 122:1013–1018CrossRefPubMed
37.
Rosenfeld PJ, Shapiro H, Tuomi L, Webster M, Elledge J, Blodi B (2011) Characteristics of patients losing vision after 2 years of monthly dosing in the phase III ranibizumab clinical trials. Ophthalmology 118:523–530CrossRefPubMed
38.
Delori FC, Fleckner MR, Goger DG, Weiter JJ, Dorey CK (2000) Autofluorescence distribution associated with drusen in age-related macular degeneration. Invest Ophthalmol Vis Sci 41:496–504PubMed
Metadata
Title
Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD)
Authors
Zhaojiang Du
Xuemei Wu
Meixia Song
Peng Li
Li Wang
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 12/2016
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-016-3508-6

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