# Role of Macrophages in Age-Related Macular Degeneration

> **NIH VA I01** · DURHAM VA MEDICAL CENTER · 2020 · —

## Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the
US and in more than a million veterans over the age of 45, resulting in a tremendous burden of care. The
objective of this proposed project is to investigate the role of retinal macrophages and relationship to functional
and structural biomarkers of disease progression in dry age-related macular degeneration (AMD), the most
common form of AMD (85%) and currently without cures. Development of retinal imaging and blood-based
biomarkers to identify individuals with HRD who will progress to NVAMD and GA is important, as these
are required to design clinical trials of novel AMD therapies that will benefit the VA population. Our
established team combines expertise in retinal ophthalmology and physiology, immunology, pathology,
bioengineering and biostatistics, with a track record of studying the pathobiology and the various classes of
biomarkers of AMD.
 Our hypothesis is that infiltration of CD163+ macrophages into the outer retina in patients with
intermediate dry AMD will correlate with synaptic defects, possibly explaining the loss of visual function in these
patients. We will assess whether infiltrating subretinal macrophages may be associated or may themselves
represent the spectral domain optical coherence tomography (SD-OCT) biomarkers of disease progression,
specifically reticular pseudodrusen and hyper-reflective foci. We will also evaluate whether high frequency of
peripheral blood CD163+ monocytes will correlate with visual dysfunction and retinal imaging biomarkers,
suggesting that retinal CD163+ macrophages are derived from recruited circulating CD163+ monocytes. In SA1,
using histopathological analysis of postmortem eyes with intermediate AMD with high risk drusen, we will
demonstrate that high frequency of outer retinal and subretinal macrophages is associated with markers of retinal
damage (especially disrupted photoreceptor synapses) as compared to age-matched control eyes and with
imaging markers of reticular pseudodrusen. In SA2, using analysis of circulating monocytes by flow cytometry
in subjects with dry AMD, we will show that high expression of peripheral blood CD163+ monocytes in
intermediate dry AMD patients will correlate with the presence of SD-OCT markers of disease progression and
visual function deficits on psychophysical tests. In SA3, we will also isolate monocytes from blood and
postmortem retina, perform analyses of gene expression and released cytokines known to mediate synaptic
dysfunction and neurotoxicity with the goal to identify factors that may contribute to loss of vision.
 This body of work will generate important new knowledge about the role of CD163+ macrophages in
 AMD patients with high-risk drusen. Our results will be able to show that infiltrating macrophages are the
 structural correlates of imaging biomarkers of disease progression in eyes with the intermediate form of the
 disease. This research will enable...

## Key facts

- **NIH application ID:** 10012438
- **Project number:** 1I01CX002116-01
- **Recipient organization:** DURHAM VA MEDICAL CENTER
- **Principal Investigator:** Eleonora Georgeta Lad
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10012438

## Citation

> US National Institutes of Health, RePORTER application 10012438, Role of Macrophages in Age-Related Macular Degeneration (1I01CX002116-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10012438. Licensed CC0.

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