Advertisement

ResearchIn-Press PreviewImmunologyOphthalmology Open Access | 10.1172/JCI205838

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

Andrew P. Voigt,1 Joyce Gong,1 Steven Droho,1 Kelly Mulfaul,2 Amrita Rajesh,1 Greta E. Forbes,1 Jacob K. Sterling,1 Miles J. Flamme-Wiese,2 Robert F. Mullins,2 and Jeremy A. Lavine1

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Voigt, A. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Gong, J. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Droho, S. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Mulfaul, K. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Rajesh, A. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Forbes, G. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Sterling, J. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Flamme-Wiese, M. in: PubMed | Google Scholar

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Mullins, R. in: PubMed | Google Scholar |

1Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

2Institute for Vision Research, The University of Iowa, Iowa City, United States of America

Find articles by Lavine, J. in: PubMed | Google Scholar

Published October 8, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI205838.
Copyright © 2026, Voigt et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 8, 2026 - Version history
View PDF
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.

Graphical Abstract
graphical abstract
Supplemental material

View

View SI Table 2: upregulated genes in each cluster in the M-eYe-verse

View SI Table 3: gene ontology (enricher) from upregulated genes in each macrophage cluster in the M-eYe-verse

View SI File 4: differential expression of CNV cells versus control cells (+ cells in underlying choroid) in the Xenium experiment

View SI File 5: GO analysis of CNV upregulated genes from SI File 4

View SI File 6: GO analysis of CC/Vein close to versus far from MMP14 expressor. GO analysis was completed for both groups (i.e., ECs close to MMP14 expressor and ECs far from MM14 expressor)

View SI Table 10: 100 custom probes used for human xenium spatial transcriptomic experiments.

Version history
  • Version 1 (October 8, 2026): In-Press Preview
Advertisement
Advertisement