July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Monocyte-related biomarkers of intermediate age-related macular degeneration
Author Affiliations & Notes
  • Vivienne Fang
    Duke University Medical Center, Durham, North Carolina, United States
  • Vaishali Oza
    Tulane University Medical School, New Orleans, Louisiana, United States
  • Sandra S Stinnett
    Duke University Medical Center, Durham, North Carolina, United States
  • Lejla Vajzovic
    Duke University Medical Center, Durham, North Carolina, United States
  • Cynthia A Toth
    Duke University Medical Center, Durham, North Carolina, United States
  • Scott W Cousins
    Duke University Medical Center, Durham, North Carolina, United States
  • Eleonora M Lad
    Duke University Medical Center, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Vivienne Fang, None; Vaishali Oza, None; Sandra Stinnett, None; Lejla Vajzovic, None; Cynthia Toth, Alcon (P), Boehringer Ingelheim (F), Genentech (F); Scott Cousins, Eyedesis (F), Heidelberg (C), Stealth Biotherapeutics (F), TheraKine (F); Eleonora Lad, Boehringer Ingelheim (F), Novartis (R), Novartis (F), Roche (F), Roche (R)
  • Footnotes
    Support  Research to Prevent Blindness Ernest & Elizabeth Althouse Special Scholar Award; Unrestricted Research to Prevent Blindness Grant; NIH Core Grant P30EY005722; NIH/NEI K23EY026988
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2976. doi:
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      Vivienne Fang, Vaishali Oza, Sandra S Stinnett, Lejla Vajzovic, Cynthia A Toth, Scott W Cousins, Eleonora M Lad; Monocyte-related biomarkers of intermediate age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2976.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The purpose of this study was to develop a flow cytometry gating strategy to investigate blood-based monocyte biomarkers of intermediate age-related macular degeneration (AMD) and determine the relationship between monocytes and structural biomarkers of disease progression on SD-OCT.

Methods : We recruited 14 patients with intermediate AMD (category 3 AREDS) and 8 normal, age-matched control subjects, enrolled as part of a prospective, observational cohort study of early AMD (NCT01822873). Subjects underwent a dilated fundus examination and retinal imaging. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples, and the samples were enriched for monocytes. The cells were stained with CD45, CD14, CD16 and CD163 antibodies and underwent flow cytometry analysis. In parallel, we performed high resolution SD-OCT and slit lamp ophthalmoscopy (SLO) on 36 postmortem eyes (22 intermediate AMD and 14 control eyes) from 22 subjects, using a custom probe specifically designed for use in autopsy eyes. The eyes were then processed for immunohistochemistry analysis of macrophage subpopulations.

Results : We have developed a flow cytometry gating strategy using the pan-monocytic marker CD45 to reliably identify PBMC subsets (classical, intermediate, and non-classical) using CD14 and CD16 expression. We found a significant difference in CD163 expression in the intermediate monocyte subset in patients with intermediate AMD vs. control patients (p=0.036 via a 2-sided Mann-Whitney U test). In postmortem intermediate AMD eyes imaged by SD-OCT and SLO, subretinal CD163+ macrophages had a morphology consistent with that of reticular pseudodrusen, a structural biomarker of disease progression.

Conclusions : Our study suggests that CD163+ cells are associated with structural biomarkers of disease progression and may represent a useful clinical blood-based biomarker on flow cytometry analysis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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