Michele C Madigan, Ceciel van den Berg,Martine J Jager, Jan M Provis
To investigate the distribution and expres-sion of macrophage phenotypes and complement acti-vation protein, C3d, in human choroid/retina inyoung, aged and AMD eyes.
Paraffin sections of central (macula andoptic disc) and peripheral choroid/retina from young(70 years, n = 4) and AMD(>70 years, n = 8) human post-mortem eyes wereco-immunolabelled with antibodies to leukocyte andmacrophage markers (CD68, CD163, Iba1 (ionizedcalcium-binding adaptor molecule 1), and CD45)and the complement activation component, C3d.Localisation and distribution of antibodies was assessedin choroid/retina using immunofluorescence andconfocal microscopy. Counts of macrophage sub-populations were compared in central and peripheralchoroid for each group.
Heterogeneous populations of macro-phages were found in the choroid/retina of all groups.Iba1+ and CD45+ retinal microglia and macrophages,and choroidal macrophages were observed in all eyes.In AMD eyes, Iba1+ and CD45+ cells were seen in thesubretinal space amongst photoreceptors, as well as ininner retina Compared to young eyes, aged and AMDspecimens showed increased numbers of CD163+macrophages (M2, proangiogenic) in the choroid, andin central versus peripheral retina. Fewer CD68+ cellswere seen in all specimens, regardless of age orlocation. C3d in young, aged and AMD eyes wasimmunolocalised to drusen, and in Bruch’s membraneand surrounding the choriocapillaris, most extensivelyin aged and AMD eyes.
Activation of the alternative comple-ment pathway is implicated in AMD, and evidenced bychanges in macrophage phenotypes at the choroidal/retinal interface in this sample of human eyes.