Immunology and Age-Related Macular Degeneration

  • Philip L. Penfold
  • James Wong
  • Diana van Driel
  • Jan M. Provis
  • Michele C. Madigan


Macular Degeneration Triamcinolone Acetonide Outer Nuclear Layer Glia Limitans Retinal Microglia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambati J, Anand A, Sakurai E, Fernandez S, Lynn B, Kuziel W, Rollins B, Ambati B (2003) An animal model of age-related macular degeneration in senescent Ccl-2 or Ccr-2 deficient mice. Nat Med 9: 1390–1397CrossRefPubMedGoogle Scholar
  2. Anderson DH, Johnson LV, Schneider BL, Nealson M, Mullins RF, Hageman GS (1999) Age-related maculopathy: a model of drusen biogenesis. Invest Ophthalmol Vis Sci 40: 922 (Abstract 4863)Google Scholar
  3. Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134: 411–431CrossRefPubMedGoogle Scholar
  4. Bressler SB, Maguire MG, Bressler NM, Fine SL (1990) Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study Group. Arch Ophthalmol 108: 1442–1447PubMedGoogle Scholar
  5. Bressler N, Bressler S, Alexander J, Javornik N, Fine S, Murphy R (1991) Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center. Arch Ophthalmol 109: 211–215PubMedGoogle Scholar
  6. Broderick C, Duncan L, Taylor N, Dick AD (2000) IFN-gamma and LPS-mediated IL-10-dependent suppression of retinal microglial activation. Invest Ophthalmol Vis Sci 41: 2613–2622PubMedGoogle Scholar
  7. Broderick C, Hoek RM, Forrester JV, Liversidge J, Sedgwick JD, Dick AD (2002) Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. Am J Pathol 161: 1669–1677PubMedGoogle Scholar
  8. Chang B, Yannuzzi LA, Ladas ID, Guyer DR, Slakter JS, Sorenson JA (1995) Choroidal neovascularization in second eyes of patients with unilateral exudative age-related macular degeneration. Ophthalmology 102: 1380–1386PubMedGoogle Scholar
  9. Chang AA, Morse LS, Handa JT, Morales RB, Tucker R, Hjelmeland L, Yannuzzi LA (1998) Histologic localization of indocyanine green dye in aging primate and human ocular tissues with clinical angiographic correlation. Ophthalmology 105: 1060–1068CrossRefPubMedGoogle Scholar
  10. Chang AA, Guyer DR, Orlock DR, Yannuzzi LA (2003) Age-dependent variations in the drusen fluorescence on indocyanine green angiography. Clin Exp Ophthalmol 31: 300–304Google Scholar
  11. Chan-Ling T, Halasz P, Stone J (1990) Development of retinal vasculature in the cat: processes and mechanisms. Curr Eye Res 9: 459–478PubMedGoogle Scholar
  12. Chen H, Wu L, Pan S, Wu DZ (1993) An immunologic study on age-related macular degeneration. Yan Ke Xue Bao 9: 113–120PubMedGoogle Scholar
  13. 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: 14682–14687CrossRefPubMedGoogle Scholar
  14. Curcio CA, Allen KA (1990) Topography of ganglion cells in human retina. J Comp Neurol 300: 5–25CrossRefPubMedGoogle Scholar
  15. Curcio CA, Saunders PL, Younger PW, Malek G (2000) Peripapillary chorioretinal atrophy: Bruch’s membrane changes and photoreceptor loss. Ophthalmology 107: 334–343CrossRefPubMedGoogle Scholar
  16. Devine I, Lightman SI, Greenwood J (1996) Role of LFA-1, ICAM-1, VLA-4 and VCAM-1 in lymphocyte migration across retinal pigment epithelial monolayers in vitro. Immunology 88: 456–462CrossRefPubMedGoogle Scholar
  17. Diaz CM, Penfold PL, Provis JM (1998) Modulation of the resistance of a human endothelial cell line by human retinal glia. Aust NZ J Ophthalmol 26[Suppl 1]: 62–64Google Scholar
  18. Diaz-Araya CM, Provis JM, Penfold PL, Billson FA (1995) Development of microglial topography in human retina. J Comp Neurol 363: 53–68CrossRefPubMedGoogle Scholar
  19. Dick AD, Pell M, Brew BJ, Foulcher E, Sedgwick JD (1997) Direct ex vivo flow cytometric analysis of human microglial cell CD4 expression: examination of central nervous system biopsy specimens from HIV-seropositive patients and patients with other neurological disease. Aids 11: 1699–1708CrossRefPubMedGoogle Scholar
  20. Dickson DW (1986) Multinucleated giant cells in aquired immunodeficiency syndrome encephalopathy. Origin from endogenous microglia? Arch Pathol Lab Med 110: 967–968PubMedGoogle Scholar
  21. 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: 3586–3592PubMedGoogle Scholar
  22. Fine SL, Berger JW, Maguire MG, Ho AC (2000) Age-related macular degeneration. N Engl J Med 342: 483–492PubMedCrossRefGoogle Scholar
  23. Freund KB, Yannuzzi LA, Sorenson JA (1993) Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol 115: 788–791Google Scholar
  24. Gass J (1973) Drusen and disciform macular detachment and degeneration. Arch Ophthalmol 90: 206–217PubMedGoogle Scholar
  25. Graeber MB (1993) Microglia, macrophages and the blood-brain barrier. Clin Neuropathol 12: 296–297PubMedGoogle Scholar
  26. Greenwood J, Penfold P, Provis J (2000) Evidence for the intrinsic innervation of retinal vessels: anatomical substrate of autoregulation in the retina? In: Burnstock G, Sillito A (eds) Innervation of the Eye. Nervous Control of the Eye, vol 13, chap 5. Harwood Academic, London, pp 155–170Google Scholar
  27. Grunwald JE, Hariprasad SM, DuPont J, Maguire MG, Fine SL, Brucker AJ, Maguire AM, Ho AC (1998) Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci 39: 385–390PubMedGoogle Scholar
  28. 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: 463–471CrossRefPubMedGoogle Scholar
  29. Gurne DH, Tso MO, Edward DP, Ripps H (1991) Antiretinal antibodies in serum of patients with age-related macular degeneration. Ophthalmology 98: 602–607PubMedGoogle Scholar
  30. Haab O (1885) Erkrankungen der macula lutea. Centralblat Augenheilkd 9: 384–391Google Scholar
  31. Hageman GS, Luthert PJ, Victor Chong NH, 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 Ret Eye Res 20: 705–732Google Scholar
  32. Heidenkummer HP, Kampik A (1995) Surgical extraction of subretinal pseudotumors in age-related macular degeneration. Clinical, morphologic and immunohistochemical results. Ophthalmologe 92: 631–639PubMedGoogle Scholar
  33. Holt PG, Degebrodt A, O’Leary C, Krska K, Plozza T (1985) T cell activation by antigen-presenting cells from lung tissue digests: suppression by endogenous macrophages. Clin Exp Immunol 62: 586–593PubMedGoogle Scholar
  34. Hutchinson AK, Grossniklaus HE, Capone A (1993) Giant-cell reaction in surgically excised subretinal neovascular membrane. Arch Ophthalmol 111: 734–735PubMedGoogle Scholar
  35. 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: 441–449CrossRefPubMedGoogle Scholar
  36. Jones S (1999) Almost like a whale. Doubleday, LondonGoogle Scholar
  37. Killingsworth MC, Sarks SH (1982) Giant cells in disciform macular degeneration of the human eye. Micron 13: 359–360Google Scholar
  38. LaFaut BA, Bartz-Schmidt KU, Vanden Broecke C, Aisenbrey S, De Laey JJ, Heimann K (2000) Clinicopatholgical correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation. Br J Ophthalmol 84: 239–243PubMedGoogle Scholar
  39. Liew SC, Penfold PL, Provis JM, Madigan MC, Billson FA (1994) Modulation of MHC class II expression in the absence of lymphocytic infiltrates in Alzheimer’s retinae. J Neuropathol Exp Neurol 53: 150–157PubMedGoogle Scholar
  40. Lopez PF, Grossniklaus HE, Lambert HM, Aaberg TM, Capone AJ, Sternberg PJ, L’Hernault N (1991) Pathologic features of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 112: 647–656PubMedGoogle Scholar
  41. Matsubara T, Pararajasegaram G, Wu GS, Rao NA (1999) Retinal microglia differentially express phenotypic markers of antigen-presenting cells in vitro. Invest Ophthalmol Vis Sci 40: 3186–3193PubMedGoogle Scholar
  42. Nettleship E (1884) Central senile areolar choroidal atrophy. Trans Ophthalmol Soc 4: 165–166Google Scholar
  43. Neumann H (2001) Control of glial immune function by neurons. Glia 36: 191–199CrossRefPubMedGoogle Scholar
  44. Newsome DA, Swartz M, Leone NC, Hewitt AT, Wolford F, Miller ED (1986) Macular degeneration and elevated serum ceruloplasmin. Invest Ophthalmol Vis Sci 27: 1675–1680PubMedGoogle Scholar
  45. Packer O, Hendrickson AE, Curcio CA (1989) Photoreceptor topography of the retina in the adult pigtail macaque (Macaca nemestrina). J Comp Neurol 288: 165–183CrossRefPubMedGoogle Scholar
  46. Pagenstecher H, Genth C (1875) Atlas der Pathologischen Anatomie des Augapfels. Kreidel, WiesbadenGoogle Scholar
  47. Palmer HE, Zaman AG, Ellis BA, Stanford MR, Graham EM, Wallace GR (1996) Longitudinal analysis of soluble intercellular adhesion molecule 1 in retinal vasculitis. Eur J Clin Invest 26: 686–691PubMedGoogle Scholar
  48. Pauleikhoff D (1992) Drusen in Bruch’s membrane. Their significance for the pathogenesis and therapy of age-associated macular degeneration. Ophthalmologie 89: 363–386Google Scholar
  49. Pavli P, Hume DA, Van De Pol E, Doe WF (1993) Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria. Immunology 78: 132–141PubMedGoogle Scholar
  50. Penfold PL, Provis JM (1986) Cell death in human retinal development: Phagocytosis of pyknotic and apoptotic bodies by retinal cells. Graefes Arch Clin Exp Ophthalmol 224: 549–553CrossRefPubMedGoogle Scholar
  51. Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223: 69–76CrossRefPubMedGoogle Scholar
  52. Penfold PL, Killingsworth MC, Sarks SH (1986) Senile macular degeneration. The involvement of giant cells in atrophy of the retinal pigment epithelium. Invest Ophthalmol Vis Sci 27: 364–371PubMedGoogle Scholar
  53. Penfold PL, Provis JM, Billson FA (1987) Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis. Graefes Arch Clin Exp Ophthalmol 225: 70–76PubMedGoogle Scholar
  54. Penfold PL, Provis JM, Furby JH, Gatenby PA, Billson FA (1990) Autoantibodies to retinal astrocytes associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 228: 270–274CrossRefPubMedGoogle Scholar
  55. Penfold PL, Madigan MC, Provis JM (1991) Antibodies to human leucocyte antigens indicate subpopulations of microglia in human retina. Vis Neurosci 7: 383–388PubMedCrossRefGoogle Scholar
  56. Penfold PL, Provis JM, Liew SC (1993) Human retinal microglia express phenotypic characteristics in common with dendritic antigen-presenting cells. J Neuroimmunol 45: 183–191CrossRefPubMedGoogle Scholar
  57. Penfold PL, Liew SC, Madigan MC, Provis JM (1997) Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration. Invest Ophthalmol Vis Sci 38: 2125–2133PubMedGoogle Scholar
  58. Penfold PL, Wen L, Madigan MC, Gillies MC, King NJ, Provis JM (2000) Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol 121: 458–465CrossRefPubMedGoogle Scholar
  59. Penfold PL, Madigan MC, Gillies MC, Provis JM (2001a) Immunological and aetiological aspects of macular degeneration. Prog Ret Eye Res 20: 385–414Google Scholar
  60. Penfold PL, Wong JG, Gyory J, Billson FA (2001b) Effects of triamcinolone acetonide on microglial morphology and quantitative expression of MHC-II in exudative age-related macular degeneration. Clin Exp Ophthalmol 29: 188–192CrossRefGoogle Scholar
  61. Provis JM, Penfold PL, Edwards AJ, van Driel D (1995) Human retinal microglia: expression of immune markers and relationship to the glia limitans. Glia 14: 243–56CrossRefPubMedGoogle Scholar
  62. Provis JM, Diaz CM, Dreher B (1998) Ontogeny of the primate fovea: a central issue in retinal development. Prog Neurobiol 54: 549–580CrossRefPubMedGoogle Scholar
  63. Provis JM, Sandercoe T, Hendrickson AE (2000) Astrocytes and blood vessels define the foveal rim during primate retinal development. Invest Ophthalmol Vis Sci 41: 2827–2836PubMedGoogle Scholar
  64. Rohen JW, Castenholtz A (1967) Über die Zentralisation der Retina bei Primaten. Folia Primatol 5: 92–147PubMedGoogle Scholar
  65. Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J (2003a) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 3578–3585PubMedGoogle Scholar
  66. Sakurai E, Taguchi H, Anand A, Ambati BK, Gragoudas ES, Miller JW, Adamis AP, Ambati J (2003b) Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization. Invest Ophthalmol Vis Sci 44: 2743–2749PubMedGoogle Scholar
  67. Sandercoe TM, Geller SF, Hendrickson AE, Stone J, Provis JM (2003) VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: evidence of developmental hypoxia. J Comp Neurol 462: 42–54CrossRefPubMedGoogle Scholar
  68. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N (2004) Association between c-reactive protein and age-related macular degeneration. J Am Med Assoc 291: 704–710CrossRefGoogle Scholar
  69. Shimizu E, Funatsu H, Yamashita H, Yamashita T, Hori S (2002) Plasma level of interleukin-6 is an indicator for predicting diabetic macular edema. Jpn J Ophthalmol 46(1): 78–83CrossRefPubMedGoogle Scholar
  70. Slakter J, Yannuzzi LA, Schneider U, Sorenson JA, Ciardella A, Guyer DR, Spaide RF, Freund KB, Orlock DA (2000) Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration. Ophthalmology 107: 742–753CrossRefPubMedGoogle Scholar
  71. Smith W, Mitchell P, Leeder SR (1996) Smoking and age-related maculopathy. The Blue Mountains Eye Study. Arch Ophthalmol 114: 1518–1523PubMedGoogle Scholar
  72. Streilein JW, Wilbanks GA, Cousins SW (1992) Immunoregulatory mechanisms of the eye. J Neuroimmunol 39: 185–200CrossRefPubMedGoogle Scholar
  73. Sunderkotter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C (1994) Macrophages and angiogenesis. J Leuk Biol 55: 410–422Google Scholar
  74. Tonnesen MG, Anderson DC, Springer TA, Knedler A, Avdi N, Henson PM (1989) Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1,LFA-1, p150,95 glycoprotein family. J Clin Invest 83: 637–646PubMedCrossRefGoogle Scholar
  75. Trowbridge I, Thomas M (1994) CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Ann Rev Immunol 12: 85–116CrossRefGoogle Scholar
  76. Tso M (1989) Experiments on visual cells by nature and man: In search of treatment for photoreceptor degeneration. Invest Ophthalmol Vis Sci 30: 2430–2454PubMedGoogle Scholar
  77. van der Schaft TL, Mooy CM, de Bruijn WC, de Jong PT (1993) Early stages of age-related macular degeneration: an immunofluorescence and electron microscopy study. Br J Ophthalmol 77: 657–661PubMedGoogle Scholar
  78. Vinores SA, Amin A, Derevjanik NL, Green WR, Campochiaro PA (1994) Immunohistochemical localization of blood-retinal barrier breakdown sites associated with post-surgical macular oedema. Histochem J 26: 655–665PubMedGoogle Scholar
  79. Widder RA, Brunner R, Walter P, Bartz-Schmidt KU, Godehardt E, Heimann K, Borberg H (1999) Modification of vision by change in rheologic parameters in senile macular degeneration through membrane differential filtration — initial results of a randomized study. Klin Monatsbl Augenheilkd 215: 43–49PubMedCrossRefGoogle Scholar
  80. Wolin LR, Massupust LC (1970) Morphology of the primate retina. In: Noback CR, Montagna W (eds) The primate brain, vol 1. Appleton-Century-Crofts, New York, pp 1–27Google Scholar
  81. Wong J, Madigan M, Billson F, Penfold P (2001) Quantification of leucocyte common antigen (CD45) expression in macular degeneration. Invest Ophthalmol Vis Sci 42: S227Google Scholar
  82. Woollard HH (1927) The differentiation of the retina in primates. Proc Zool Soc Lond 1: 1–17Google Scholar
  83. Yang P, Chen L, Zwart R, Kijlstra A (2002) Immune cells in the porcine retina: distribution, characterization and morphological features. Invest Ophthalmol Vis Sci 43(5): 1488–1492PubMedGoogle Scholar
  84. Yannuzzi L, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund K, Sorenson J, Orlock D, Borodoker N, LuEsther T (2001) Retinal angiomatous proliferation in age-related macular degeneration. Retina 21: 416–434PubMedGoogle Scholar
  85. Zhang J, Wu G-S, Ishimoto S-I, Pararajasegaram G, Rao NA (1997) Expression of major histocompatibility complex molecules in rodent retina. Immunohistochemical study. Invest Ophthalmol Vis Sci 38: 1848–1857PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Philip L. Penfold
  • James Wong
  • Diana van Driel
  • Jan M. Provis
  • Michele C. Madigan

There are no affiliations available

Personalised recommendations