# Investigating the function and mechanism of interleukin 7 receptor-expressing pro-angiogenic macrophages during experimental choroidal neovascularization

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $400,000

## Abstract

PROJECT SUMMARY:
Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the developed world,
and is treated solely by inhibiting vascular endothelial growth factor (VEGF). Although highly effective, 15% of
patients still lose vision despite maximal anti-VEGF therapy. Thus, a critical need exists for novel non-VEGF
therapies. The complement pathway is genetically associated with AMD, macrophages express complement
proteins and receptors, and macrophages are found in surgically excised choroidal neovascularization (CNV).
Additionally, choroidal macrophage depletion results in choroidal atrophy, and both global macrophage depletion
and inhibition of classical monocyte-derived macrophages reduce experimental CNV area. Therefore,
macrophages are implicated in human CNV, steady state vascular homeostasis, and pathological choroidal
angiogenesis. However, macrophages are known to be highly heterogeneous cells that can perform many
diverse functions. Therefore, we performed single-cell RNA-sequencing on wildtype and classical monocyte-
depleted mice to investigate macrophage origin, heterogeneity, and function during laser-induced CNV. We
identified that interleukin-7 receptor (IL7R)-expressing macrophages are likely derived from classical monocytes
and display a pro-angiogenic transcriptome. Based upon these data, our central hypothesis is that IL7R+
macrophages are critical pro-angiogenic cells during CNV pathogenesis. To test this hypothesis, we formulated
the following specific aims:
1) Demonstrate that IL7R+ macrophages are necessary for CNV. In this aim, we will use Il7rCre x Rosa26GFP
 mice to fate map IL7R+ macrophages, Il7rCre x Cx3cr1iDTR mice to deplete IL7R+ macrophages, and
 Cx3cr1CrER x Il7rflox mice to knockout the IL7R. We will test the function of IL7R+ macrophages and the IL7R
 using the laser-induced CNV model.
2) Determine that IL7R+ macrophages are derived from classical monocytes and are sufficient to stimulate CNV.
 In this aim, we will use Ccr2CreER x Rosa26GFP mice to fate map classical monocytes and determine if classical
 monocytes can differentiate into IL7R+ macrophages. Furthermore, we will show that IL7R+ macrophages
 are sufficient to stimulate angiogenesis by isolating IL7R+ macrophages from mouse eyes after laser injury.
 We will then test the ability of IL7R+ vs IL7Rneg macrophages to rescue reduced CNV area in Ccr2-/- mice.
Completion of these aims will determine that IL7R+ macrophages are necessary for CNV, derived from classical
monocytes, and sufficient to stimulate angiogenesis. These data will set the stage for cell-based anti-CNV
therapies. Cell-based therapies, targeting IL7R+ macrophages, have the potential to inhibit multiple pro-
angiogenic pathways simultaneously, rather than inhibiting VEGF alone, and change the paradigm for nAMD
therapy.

## Key facts

- **NIH application ID:** 10563645
- **Project number:** 1R01EY034486-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jeremy A Lavine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10563645

## Citation

> US National Institutes of Health, RePORTER application 10563645, Investigating the function and mechanism of interleukin 7 receptor-expressing pro-angiogenic macrophages during experimental choroidal neovascularization (1R01EY034486-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10563645. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*