Abundance of infiltrating CD163+ cells in the retina of postmortem eyes with dry and neovascular age-related macular degeneration

  • Eleonora M. LadEmail author
  • Scott W. Cousins
  • John S. Van Arnam
  • Alan D. Proia
Basic Science



Prior research in animal models has suggested that retinal macrophages play an important role in age-related macular degeneration (AMD), but studies have insufficiently characterized the distribution of retinal macrophages in various stages of human AMD.


In this case series, we analyzed H&E, periodic acid-Schiff, and CD163 and CD68 immunostained slides from 56 formaldehyde-fixed, paraffin-embedded autopsy eyes of patients over age 75: 11 age-matched, normal eyes, and 45 AMD eyes.


Qualitative analysis of the macula and retinal periphery revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells. In normal eyes and eyes with thin or infrequent basal laminar deposits, CD163+ cells were restricted to the inner retina. In contrast, in AMD eyes with thick basal deposits, choroidal neovascular membranes, and geographic atrophy, qualitatively there was a marked increase in the number and size of the CD163+ cells in the outer retina, sub-retinal, and sub-retinal pigment epithelium space in the macula.


The changes in number and localization of retinal CD163+ cells in eyes with intermediate-severe AMD support a key role for macrophages in the pathogenesis and progression of the disease. A larger, quantitative study evaluating the distribution of macrophage subpopulations in postmortem AMD eyes is warranted.


Age related-macular degeneration Macrophages Inflammation Histopathology Postmortem eyes 


Conflict of interest

All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Financial disclosure

None to report


  1. 1.
    Caicedo A, Espinosa-Heidmann DG, Hamasaki D, Pina Y, Cousins SW (2005) Photoreceptor synapses degenerate early in experimental choroidal neovascularization. J Comp Neurol 483:263–277CrossRefPubMedGoogle Scholar
  2. 2.
    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 81:38–47CrossRefPubMedGoogle Scholar
  3. 3.
    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 8:119–126PubMedGoogle Scholar
  4. 4.
    Penfold PL, Gyory JF, Hunyor AB, Billson FA (1995) Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Aust N Z J Ophthalmol 23:293–298CrossRefPubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    Cao X, Shen D, Patel MM, Tuo J, Johnson TM, Olsen TW, Chan CC (2011) Macrophage polarization in the maculae of age-related macular degeneration: a pilot study. Pathol Int 61:528–535PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Sarks SH (1976) Ageing and degeneration in the macular region: a clinico-pathological study. Br J Ophthalmol 60:324–341PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    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 94:918–925CrossRefPubMedGoogle Scholar
  9. 9.
    Cherepanoff S, Hasic E, McMenamin P, Gillies M (2013) CD163+ and CD68+ cells in the adult human eye. Invest Ophthalmol Vis Sci 54(15):2048Google Scholar
  10. 10.
    Killingsworth MC, Sarks JP, Sarks SH (1990) Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye (Lond) 4(Pt 4):613–621CrossRefGoogle Scholar
  11. 11.
    Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, Matsumura M, Ogura Y, Honda Y (1999) The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci 40:1891–1898PubMedGoogle Scholar
  12. 12.
    Skeie JM, Mullins RF (2009) Macrophages in neovascular age-related macular degeneration: friends or foes? Eye (Lond) 23:747–755CrossRefGoogle Scholar
  13. 13.
    Yang P, Das PK, Kijlstra A (2000) Localization and characterization of immunocompetent cells in the human retina. Ocul Immunol Inflamm 8:149–157CrossRefPubMedGoogle Scholar
  14. 14.
    Penfold PL, Madigan MC, Provis JM (1991) Antibodies to human leucocyte antigens indicate subpopulations of microglia in human retina. Vis Neurosci 7:383–388CrossRefPubMedGoogle Scholar
  15. 15.
    Bronkhorst IH, Ly LV, Jordanova ES, Vrolijk J, Versluis M, Luyten GP, Jager MJ (2011) Detection of M2-macrophages in uveal melanoma and relation with survival. Invest Ophthalmol Vis Sci 52:643–650CrossRefPubMedGoogle Scholar
  16. 16.
    Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198–201CrossRefPubMedGoogle Scholar
  17. 17.
    Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM (2008) Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng A 14:1835–1842CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Eleonora M. Lad
    • 1
    Email author
  • Scott W. Cousins
    • 1
  • John S. Van Arnam
    • 2
  • Alan D. Proia
    • 1
    • 2
  1. 1.Department of OphthalmologyDuke University Medical CenterDurhamUSA
  2. 2.Department of PathologyDuke University Medical CenterDurhamUSA

Personalised recommendations