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Eleonora M Lad, Scott W Cousins, Sina Farsiu, Alan D Proia; Retinal Macrophages in Stages of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3535.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize retinal macrophage subpopulations in postmortem human eyes with various stages of AMD, as defined by both histopathologic staging and retinal imaging.
62 human postmortem autopsy eyes from patients over age 80 were enucleated and fixed in 4% formaldehyde. The eyes were imaged using SD-OCT (Bioptigen, Morrisville, NC) and scanning laser ophthalmoscopy (SLO)(Heidelberg Engineering, Carlsbad, CA), then paraffin embedded and sectioned for histopathology analysis. H&E and Periodic-acid Schiff stained macular sections were graded according to a new histological classification system for AMD based on the staging by Sarks (1976). Unstained paraffin macular sections were processed for immunohistochemistry (IHC) analysis for CD68 and CD163 macrophage markers, as well as CD45 pan-leukocytic marker. The use of the donor eyes for research was approved by the Institutional Review Board of the Duke University Medical Center.
Analysis of both the macula and retinal periphery revealed that normal, age-matched eyes and AMD eyes contained a large number of CD163+ and CD45+ cells. The number of CD68+ cells in the retina was significantly lower in AMD eyes and nearly negligible in normal aged eyes. In eyes with early AMD, CD163+ macrophages were restricted to the inner retina above the outer plexiform layer. In contrast, in AMD eyes with continuous basal laminar linear deposits, there was a significant increase in the number and size of the CD163+ cells in the outer retina and sub-retinal space. AMD changes observed on SD-OCT and SLO imaging correlated with histopathology findings. Subretinal macrophages in AMD eyes with intermediate-severe disease were associated with a targetoid, reticular pseudodrusen pattern on SLO and subretinal hyperreflective deposits on SD-OCT.
We report a new histologic classification system for AMD and novel observations using the macrophage marker CD163. Retinas of normal and AMD eyes contain a significantly larger number of macrophages than previously reported using prior immunohistochemical markers. Importantly, there is a striking change in the retinal distribution of macrophages in postmortem eyes with intermediate-severe AMD as compared to normal or early AMD eyes. AMD pathology including subretinal macrophages could be specifically detected and localized by SD-OCT and SLO imaging in human postmortem eyes.
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