Monocyte-derived pro-angiogenic ocular macrophages identified by spatial transcriptomics are essential for choroidal neovascularization

Andrew P Voigt; Joyce Gong; Steven Droho; Kelly Mulfaul; Amrita Rajesh; Greta E Forbes; Jacob K Sterling; Miles J Flamme-Wiese; Robert F Mullins; Jeremy A Lavine

doi:10.1172/JCI205838

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Monocyte-derived pro-angiogenic ocular macrophages identified by spatial transcriptomics are essential for choroidal neovascularization

Journal article

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Monocyte-derived pro-angiogenic ocular macrophages identified by spatial transcriptomics are essential for choroidal neovascularization

Andrew P Voigt, Joyce Gong, Steven Droho, Kelly Mulfaul, Amrita Rajesh, Greta E Forbes, Jacob K Sterling, Miles J Flamme-Wiese, Robert F Mullins and Jeremy A Lavine

The Journal of clinical investigation

10/08/2026

DOI: 10.1172/JCI205838

PMID: 42848455

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Abstract

The human retina and underlying choroid have multiple well-organized vascular layers. However, retinal and choroidal neovascularization can develop in diseases such as diabetic retinopathy or neovascular age-related macular degeneration, which can result in destructive vision loss. Ocular macrophages are implicated in the pathogenesis of such neovascular diseases. To identify a potential pro-angiogenic macrophage subtype, we integrated 13 single-cell RNA sequencing datasets from human and mouse eyes comprising 173 unique samples. From 99,184 mononuclear phagocytes, we identified a single macrophage subtype with high expression of SPP1, FABP5, and IL7R that was over-represented from neovascular disease samples. We fate mapped these cells and specifically depleted them, showing that they are monocyte-derived and necessary for laser-induced choroidal neovascularization in mice. Finally, we performed a high-resolution spatial RNA sequencing experiment on six human donors and found that the pro-angiogenic macrophage subtype localized to human choroidal neovascular membranes. These macrophages and other cells in neovascular membranes expressed MMP14, a potential therapeutic target, and MMP14 inhibition decreased choroidal neovascularization in mice. Collectively, we show that this Monocyte-derived Pro-angiogenic Ocular Macrophage (MoPOM) subtype is upregulated in multiple ocular neovascular diseases across species, necessary for choroidal neovascularization, and is a potential therapeutic target to reduce destructive angiogenesis in the eye.

Angiogenesis

Immunology

Ophthalmology

Macrophages

Details

Title: Subtitle: Monocyte-derived pro-angiogenic ocular macrophages identified by spatial transcriptomics are essential for choroidal neovascularization
Creators: Andrew P Voigt - Northwestern University
Joyce Gong - Northwestern University
Steven Droho - Northwestern University
Kelly Mulfaul - University of Iowa
Amrita Rajesh - Northwestern University
Greta E Forbes - Northwestern University
Jacob K Sterling - Northwestern University
Miles J Flamme-Wiese - University of Iowa
Robert F Mullins - University of Iowa
Jeremy A Lavine - Northwestern University
Resource Type: Journal article
Publication Details: The Journal of clinical investigation
DOI: 10.1172/JCI205838
PMID: 42848455
NLM abbreviation: J Clin Invest
ISSN: 1558-8238
eISSN: 1558-8238
Publisher: American Society for Clinical Investigation
Language: English
Electronic publication date: 10/08/2026
Academic Unit: The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9985244643202771

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