Skip to main content

Advertisement

Springer Nature Link
Log in

Immunopathological aspects of age-related macular degeneration

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Klein R, Peto T, Bird A, Vannewkirk MR (2004) The epidemiology of age-related macular degeneration. Am J Ophthalmol 137:486–495

    Article  PubMed  Google Scholar 

  2. Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572

    Article  PubMed  Google Scholar 

  3. Klein R, Klein BE, Linton KL (1992) Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 99:933–943

    PubMed  CAS  Google Scholar 

  4. Klein R, Klein BE, Jensen SC, Meuer SM (1997) The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 104:7–21

    PubMed  CAS  Google Scholar 

  5. Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol 48:257–293

    Article  PubMed  Google Scholar 

  6. Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115–134

    Article  PubMed  CAS  Google Scholar 

  7. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL III (2005) Risk factors for the incidence of advanced age-related macular degeneration in the age-related eye disease study (AREDS) AREDS report no. 19. Ophthalmology 112:533–539

    Article  PubMed  Google Scholar 

  8. Scholl HP, Fleckenstein M, Charbel IP, Keilhauer C, Holz FG, Weber BH (2007) An update on the genetics of age-related macular degeneration. Mol Vis 13:196–205

    PubMed  CAS  Google Scholar 

  9. Taylor HR, Munoz B, West S, Bressler NM, Bressler SB, Rosenthal FS (1990) Visible light and risk of age-related macular degeneration. Trans Am Ophthalmol Soc 88:163–173

    PubMed  CAS  Google Scholar 

  10. Dastgheib K, Green WR (1994) Granulomatous reaction to Bruch’s membrane in age-related macular degeneration. Arch Ophthalmol 112:813–818

    PubMed  CAS  Google Scholar 

  11. Grossniklaus HE, Ling JX, Wallace TM, Dithmar S, Lawson DH, Cohen C, Elner VM, Elner SG, Sternberg P Jr. (2002) Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis 8:119–126

    PubMed  CAS  Google Scholar 

  12. Gupta N, Brown KE, Milam AH (2003) Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res 76:463–471

    Article  PubMed  CAS  Google Scholar 

  13. Penfold PL, Madigan MC, Gillies MC, Provis JM (2001) Immunological and aetiological aspects of macular degeneration. Prog Retin Eye Res 20:385–414

    Article  PubMed  CAS  Google Scholar 

  14. Walport MJ (2001) Complement. First of two parts. N Engl J Med 344:1058–1066

    Article  PubMed  CAS  Google Scholar 

  15. Walport MJ (2001) Complement. Second of two parts. N Engl J Med 344:1140–1144

    Article  PubMed  CAS  Google Scholar 

  16. Brito BE, O’Rourke LM, Pan Y, Anglin J, Planck SR, Rosenbaum JT (1999) IL-1 and TNF receptor-deficient mice show decreased inflammation in an immune complex model of uveitis. Invest Ophthalmol Vis Sci 40:2583–2589

    PubMed  CAS  Google Scholar 

  17. Zipfel PF, Heinen S, Jozsi M, Skerka C (2006) Complement and diseases: defective alternative pathway control results in kidney and eye diseases. Mol Immunol 43:97–106

    Article  PubMed  CAS  Google Scholar 

  18. Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14:835–846

    PubMed  CAS  Google Scholar 

  19. Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang K, Ambati BK, Baffi JZ, Ambati J (2006) Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci USA 103:2328–2333

    Article  PubMed  CAS  Google Scholar 

  20. Johnson LV, Ozaki S, Staples MK, Erickson PA, Anderson DH (2000) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res 70:441–449

    Article  PubMed  CAS  Google Scholar 

  21. Hageman GS, Mullins RF, Russell SR, Johnson LV, Anderson DH (1999) Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells. FASEB J 13:477–484

    PubMed  CAS  Google Scholar 

  22. Johnson LV, Leitner WP, Staples MK, Anderson DH (2001) Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res 73:887–896

    Article  PubMed  CAS  Google Scholar 

  23. Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA 99:14682–14687

    Article  PubMed  CAS  Google Scholar 

  24. Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT (2007) Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 357:553–561

    Article  PubMed  CAS  Google Scholar 

  25. Alsenz J, Schulz TF, Lambris JD, Sim RB, Dierich MP (1985) Structural and functional analysis of the complement component factor H with the use of different enzymes and monoclonal antibodies to factor H. Biochem J 232:841–850

    PubMed  CAS  Google Scholar 

  26. Rodriguez de CS, Esparza-Gordillo J, Goicoechea de JE, Lopez-Trascasa M, Sanchez-Corral P (2004) The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 41:355–367

    Article  CAS  Google Scholar 

  27. Prosser BE, Johnson S, Roversi P, Herbert AP, Blaum BS, Tyrrell J, Jowitt TA, Clark SJ, Tarelli E, Uhrin D, Barlow PN, Sim RB, Day AJ, Lea SM (2007) Structural basis for complement factor H linked age-related macular degeneration. J Exp Med 204:2277–2283

    Article  PubMed  CAS  Google Scholar 

  28. Mandal MN, Ayyagari R (2006) Complement factor H: spatial and temporal expression and localization in the eye. Invest Ophthalmol Vis Sci 47:4091–4097

    Article  PubMed  Google Scholar 

  29. Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK, Klein BE, Klein R, Lee KE, Majewski J, Schultz DW, Klein ML, Seddon JM, Santangelo SL, Weeks DE, Conley YP, Mah TS, Schmidt S, Haines JL, Pericak-Vance MA, Gorin MB, Schulz HL, Pardi F, Lewis CM, Weber BH (2005) Meta-analysis of genome scans of age-related macular degeneration. Hum Mol Genet 14:2257–2264

    Article  PubMed  CAS  Google Scholar 

  30. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308:385–389

    Article  PubMed  CAS  Google Scholar 

  31. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102:7227–7232

    Article  PubMed  CAS  Google Scholar 

  32. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308:419–421

    Article  PubMed  CAS  Google Scholar 

  33. Edwards AO, Ritter R III, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424

    Article  PubMed  CAS  Google Scholar 

  34. Thakkinstian A, Han P, McEvoy M, Smith W, Hoh J, Magnusson K, Zhang K, Attia J (2006) Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration. Hum Mol Genet 15:2784–2790

    Article  PubMed  CAS  Google Scholar 

  35. Tuo J, Ning B, Bojanowski CM, Lin ZN, Ross RJ, Reed GF, Shen D, Jiao X, Zhou M, Chew EY, Kadlubar FF, Chan CC (2006) Synergic effect of polymorphisms in ERCC6 5¢¢ flanking region and complement factor H on age-related macular degeneration predisposition. Proc Natl Acad Sci USA 103:9256–9261

    Article  PubMed  CAS  Google Scholar 

  36. Ross RJ, Bojanowski CM, Wang JJ, Chew EY, Rochtchina E, Ferris FL III, Mitchell P, Chan CC, Tuo J (2007) The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci 48:1128–1132

    Article  PubMed  Google Scholar 

  37. Haddad S, Chen CA, Santangelo SL, Seddon JM (2006) The genetics of age-related macular degeneration: a review of progress to date. Surv Ophthalmol 51:316–363

    Article  PubMed  Google Scholar 

  38. Skerka C, Lauer N, Weinberger AA, Keilhauer CN, Suhnel J, Smith R, Schlotzer-Schrehardt U, Fritsche L, Heinen S, Hartmann A, Weber BH, Zipfel PF (2007) Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration. Mol Immunol 44:3398–3406

    Article  PubMed  CAS  Google Scholar 

  39. Laine M, Jarva H, Seitsonen S, Haapasalo K, Lehtinen MJ, Lindeman N, Anderson DH, Johnson PT, Jarvela I, Jokiranta TS, Hageman GS, Immonen I, Meri S (2007) Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein. J Immunol 178:3831–3836

    PubMed  CAS  Google Scholar 

  40. Chen M, Forrester JV, Xu H (2007) Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. Exp Eye Res 84:635–645

    Article  PubMed  CAS  Google Scholar 

  41. Zipfel PF, Hellwage J, Friese MA, Hegasy G, Jokiranta ST, Meri S (1999) Factor H and disease: a complement regulator affects vital body functions. Mol Immunol 36:241–248

    Article  PubMed  CAS  Google Scholar 

  42. Tuo J, Bojanowski CM, Zhou M, Shen D, Ross RJ, Rosenberg KI, Cameron DJ, Yin C, Kowalak JA, Zhuang Z, Zhang K, Chan CC (2007) Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration. Invest Ophthalmol Vis Sci 48:3827–3836

    Article  PubMed  Google Scholar 

  43. Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 38:458–462

    Article  PubMed  CAS  Google Scholar 

  44. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N (2004) Association between C-reactive protein and age-related macular degeneration. JAMA 291:704–710

    Article  PubMed  CAS  Google Scholar 

  45. Boekhoorn SS, Vingerling JR, Witteman JC, Hofman A, de Jong PT (2007) C-reactive protein level and risk of aging macula disorder: the Rotterdam study. Arch Ophthalmol 125:1396–1401

    Article  PubMed  CAS  Google Scholar 

  46. Zhou J, Jang YP, Kim SR, Sparrow JR (2006) Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci USA 103:16182–16187

    Article  PubMed  CAS  Google Scholar 

  47. Rogers J, Cooper NR, Webster S, Schultz J, McGeer PL, Styren SD, Civin WH, Brachova L, Bradt B, Ward P (1992) Complement activation by beta-amyloid in Alzheimer disease. Proc Natl Acad Sci USA 89:10016–10020

    Article  PubMed  CAS  Google Scholar 

  48. Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH (2002) The Alzheimer’s A beta-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 99:11830–11835

    Article  PubMed  CAS  Google Scholar 

  49. Tobe T, Ortega S, Luna JD, Ozaki H, Okamoto N, Derevjanik NL, Vinores SA, Basilico C, Campochiaro PA (1998) Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model. Am J Pathol 153:1641–1646

    PubMed  CAS  Google Scholar 

  50. Bora PS, Sohn JH, Cruz JM, Jha P, Nishihori H, Wang Y, Kaliappan S, Kaplan HJ, Bora NS (2005) Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization. J Immunol 174:491–497

    PubMed  CAS  Google Scholar 

  51. Bora NS, Kaliappan S, Jha P, Xu Q, Sohn JH, Dhaulakhandi DB, Kaplan HJ, Bora PS (2006) Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H. J Immunol 177:1872–1878

    PubMed  CAS  Google Scholar 

  52. Coffey PJ, Gias C, McDermott CJ, Lundh P, Pickering MC, Sethi C, Bird A, Fitzke FW, Maass A, Chen LL, Holder GE, Luthert PJ, Salt TE, Moss SE, Greenwood J (2007) Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction. Proc Natl Acad Sci USA 104:16651–16656

    Article  PubMed  CAS  Google Scholar 

  53. Bora NS, Kaliappan S, Jha P, Xu Q, Sivasankar B, Harris CL, Morgan BP, Bora PS (2007) CD59, a complement regulatory protein, controls choroidal neovascularization in a mouse model of wet-type age-related macular degeneration. J Immunol 178:1783–1790

    PubMed  CAS  Google Scholar 

  54. Chan CC, Li Q (1998) Immunopathology of uveitis. Br J Ophthalmol 82:91–96

    Article  PubMed  CAS  Google Scholar 

  55. Smith JR, Hart PH, Williams KA (1998) Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis. Immunol Cell Biol 76:497–512

    Article  PubMed  CAS  Google Scholar 

  56. Adamus G, Chan CC (2002) Experimental autoimmune uveitides: multiple antigens, diverse diseases. Int Rev Immunol 21:209–229

    Article  PubMed  CAS  Google Scholar 

  57. Ooi KG, Galatowicz G, Calder VL, Lightman SL (2006) Cytokines and chemokines in uveitis: is there a correlation with clinical phenotype? Clin Med Res 4:294–309

    Article  PubMed  CAS  Google Scholar 

  58. Lopez PF, Grossniklaus HE, Lambert HM, Aaberg TM, Capone A Jr., Sternberg P Jr., L’Hernault N (1991) Pathologic features of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 112:647–656

    PubMed  CAS  Google Scholar 

  59. Forrester JV (2003) Macrophages eyed in macular degeneration. Nat Med 9:1350–1351

    Article  PubMed  CAS  Google Scholar 

  60. Kuziel WA, Morgan SJ, Dawson TC, Griffin S, Smithies O, Ley K, Maeda N (1997) Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc Natl Acad Sci USA 94:12053–12058

    Article  PubMed  CAS  Google Scholar 

  61. Lu B, Rutledge BJ, Gu L, Fiorillo J, Lukacs NW, Kunkel SL, North R, Gerard C, Rollins BJ (1998) Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med 187:601–608

    Article  PubMed  CAS  Google Scholar 

  62. Bojanowski CM, Shen D, Chew EY, Ning B, Csaky KG, Green WR, Chan CC, Tuo J (2006) An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation. Environ Mol Mutagen 47:594–602

    Article  PubMed  CAS  Google Scholar 

  63. 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 9:1390–1397

    Article  PubMed  CAS  Google Scholar 

  64. Csaky K, Baffi J, Chan CC, Byrnes GA (2004) Clinicopathologic correlation of progressive fibrovascular proliferation associated with occult choroidal neovascularization in age-related macular degeneration. Arch Ophthalmol 122:650–652

    Article  PubMed  Google Scholar 

  65. Kamei M, Yoneda K, Kume N, Suzuki M, Itabe H, Matsuda K, Shimaoka T, Minami M, Yonehara S, Kita T, Kinoshita S (2007) Scavenger receptors for oxidized lipoprotein in age-related macular degeneration. Invest Ophthalmol Vis Sci 48:1801–1807

    Article  PubMed  Google Scholar 

  66. 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 13:772–778

    PubMed  CAS  Google Scholar 

  67. 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 44:3586–3592

    Article  PubMed  Google Scholar 

  68. Sakurai E, Anand A, Ambati BK, van RN, Ambati J (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3578–3585

    Article  PubMed  Google Scholar 

  69. Apte RS, Richter J, Herndon J, Ferguson TA (2006) Macrophages inhibit neovascularization in a murine model of age-related macular degeneration. PloS Med 3:e310

    Article  PubMed  CAS  Google Scholar 

  70. Tsutsumi C, Sonoda KH, Egashira K, Qiao H, Hisatomi T, Nakao S, Ishibashi M, Charo IF, Sakamoto T, Murata T, Ishibashi T (2003) The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization. J Leukoc Biol 74:25–32

    Article  PubMed  CAS  Google Scholar 

  71. Yamada K, Sakurai E, Itaya M, Yamasaki S, Ogura Y (2007) Inhibition of laser-induced choroidal neovascularization by atorvastatin by downregulation of monocyte chemotactic protein-1 synthesis in mice. Invest Ophthalmol Vis Sci 48:1839–1843

    Article  PubMed  Google Scholar 

  72. Chen J, Connor KM, Smith LE (2007) Overstaying their welcome: defective CX3CR1 microglia eyed in macular degeneration. J Clin Invest 117:2758–2762

    Article  PubMed  CAS  Google Scholar 

  73. 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 25:677–686

    Article  PubMed  CAS  Google Scholar 

  74. Dick AD, Forrester JV, Liversidge J, Cope AP (2004) The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU). Prog Retin Eye Res 23:617–637

    Article  PubMed  CAS  Google Scholar 

  75. Dick AD, Ford AL, Forrester JV, Sedgwick JD (1995) Flow cytometric identification of a minority population of MHC class II positive cells in the normal rat retina distinct from CD45lowCD11b/c+CD4low parenchymal microglia. Br J Ophthalmol 79:834–840

    Article  PubMed  CAS  Google Scholar 

  76. Rao NA, Kimoto T, Zamir E, Giri R, Wang R, Ito S, Pararajasegaram G, Read RW, Wu GS (2003) Pathogenic role of retinal microglia in experimental uveoretinitis. Invest Ophthalmol Vis Sci 44:22–31

    Article  PubMed  Google Scholar 

  77. Langmann T (2007) Microglia activation in retinal degeneration. J Leukoc Biol 81:1345–1351

    Article  PubMed  CAS  Google Scholar 

  78. Roque RS, Rosales AA, Jingjing L, Agarwal N, Al-Ubaidi MR (1999) Retina-derived microglial cells induce photoreceptor cell death in vitro. Brain Res 836:110–119

    Article  PubMed  CAS  Google Scholar 

  79. Fong AM, Robinson LA, Steeber DA, Tedder TF, Yoshie O, Imai T, Patel DD (1998) Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med 188:1413–1419

    Article  PubMed  CAS  Google Scholar 

  80. Silverman MD, Zamora DO, Pan Y, Texeira PV, Baek SH, Planck SR, Rosenbaum JT (2003) Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells. Invest Ophthalmol Vis Sci 44:1608–1615

    Article  PubMed  Google Scholar 

  81. Tuo J, Smith BC, Bojanowski CM, Meleth AD, Gery I, Csaky KG, Chew EY, Chan CC (2004) The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J 18:1297–1299

    PubMed  CAS  Google Scholar 

  82. Chan CC, Tuo J, Bojanowski CM, Csaky KG, Green WR (2005) Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration. Histol Histopathol 20:857–863

    PubMed  CAS  Google Scholar 

  83. McDermott DH, Fong AM, Yang Q, Sechler JM, Cupples LA, Merrell MN, Wilson PW, D’Agostino RB, O’Donnell CJ, Patel DD, Murphy PM (2003) Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans. J Clin Invest 111:1241–1250

    PubMed  CAS  Google Scholar 

  84. Moatti D, Faure S, Fumeron F, Amara M, Seknadji P, McDermott DH, Debre P, Aumont MC, Murphy PM, de PD, Combadiere C (2001) Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease. Blood 97:1925–1928

    Article  PubMed  CAS  Google Scholar 

  85. Combadiere C, Feumi C, Raoul W, Keller N, Rodero M, Pezard A, Lavalette S, Houssier M, Jonet L, Picard E, Debre P, Sirinyan M, Deterre P, Ferroukhi T, Cohen SY, Chauvaud D, Jeanny JC, Chemtob S, Behar-Cohen F, Sennlaub F (2007) CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest 117:2920–2928

    Article  PubMed  CAS  Google Scholar 

  86. Xu H, Chen M, Manivannan A, Lois N, Forrester JV (2007) Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice. Aging Cell 7:58–68

    Article  PubMed  CAS  Google Scholar 

  87. Kalayoglu MV, Galvan C, Mahdi OS, Byrne GI, Mansour S (2003) Serological association between Chlamydia pneumoniae infection and age-related macular degeneration. Arch Ophthalmol 121:478–482

    Article  PubMed  Google Scholar 

  88. Robman L, Mahdi O, McCarty C, Dimitrov P, Tikellis G, McNeil J, Byrne G, Taylor H, Guymer R (2005) Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration. Am J Epidemiol 161:1013–1019

    Article  PubMed  Google Scholar 

  89. Kalayoglu MV, Bula D, Arroyo J, Gragoudas ES, D’Amico D, Miller JW (2005) Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 243:1080–1090

    Article  PubMed  Google Scholar 

  90. Kessler W, Jantos CA, Dreier J, Pavlovic S (2006) Chlamydia pneumoniae is not detectable in subretinal neovascular membranes in the exudative stage of age-related macular degeneration. Acta Ophthalmol Scand 84:333–337

    Article  PubMed  Google Scholar 

  91. Robman L, Mahdi OS, Wang JJ, Burlutsky G, Mitchell P, Byrne G, Guymer R, Taylor H (2007) Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci 48:4007–4011

    Article  PubMed  Google Scholar 

  92. Abdelrahman YM, Belland RJ (2005) The chlamydial developmental cycle. FEMS Microbiol Rev 29:949–959

    Article  PubMed  CAS  Google Scholar 

  93. Yamaguchi H, Haranaga S, Widen R, Friedman H, Yamamoto Y (2002) Chlamydia pneumoniae infection induces differentiation of monocytes into macrophages. Infect Immun 70:2392–2398

    Article  PubMed  CAS  Google Scholar 

  94. MacIntyre A, Abramov R, Hammond CJ, Hudson AP, Arking EJ, Little CS, Appelt DM, Balin BJ (2003) Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells. J Neurosci Res 71:740–750

    Article  PubMed  CAS  Google Scholar 

  95. Yoshida T, Koide N, Mori I, Ito H, Yokochi T (2006) Chlamydia pneumoniae infection enhances lectin-like oxidized low-density lipoprotein receptor (LOX-1) expression on human endothelial cells. FEMS Microbiol Lett 260:17–22

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Immunopathology, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA

    Mrinali Patel & Chi-Chao Chan

  2. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Mrinali Patel

Authors
  1. Mrinali Patel
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Chi-Chao Chan
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Chi-Chao Chan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patel, M., Chan, CC. Immunopathological aspects of age-related macular degeneration. Semin Immunopathol 30, 97–110 (2008). https://doi.org/10.1007/s00281-008-0112-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-008-0112-9

Keywords