Macrophage-derived VEGFA helps maintain eye fluid pressure during aging
In aged mice and humans, macrophages cluster near Schlemm's canal to preserve aqueous humor outflow through compensatory growth factor signaling.
bioRxiv : the preprint server for biology · Kiyota N et al. · Paper published 11 Sep 2026
In mice and human tissues, researchers investigated how the aging ocular drainage system maintains intraocular pressure homeostasis. Imaging revealed that aging reduced the size of Schlemm's canal and increased peri-canal macrophage accumulation in both species. Single-cell RNA sequencing of mouse ocular angle tissues showed immunomodulatory transcriptional changes in aged Schlemm's canal endothelial cells. In aged and Tie2-haploinsufficient mice, computational analysis predicted increased VEGFA-VEGFR signaling between macrophages and endothelial cells. Genetically deleting Vegfa in CX3CR1-positive macrophages elevated intraocular pressure and reduced outflow facility in nine-month-old mice. Furthermore, gene therapy enhancing TIE2 activity protected wild-type mice against age-related Schlemm's canal niche changes.
Why it matters
The findings reveal an immune-vascular compensatory mechanism that helps stabilize fluid drainage in the eye during normal aging. They also point to TIE2 signaling as a potential target to protect ocular drainage structures from age-related degradation.
Caveats
This work was released as a preprint and has not yet undergone peer review. Key functional manipulations, including macrophage gene deletion and gene therapy, were conducted only in mouse models.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
VEGFA-Positive Macrophages Regulate Aqueous Humor Outflow in Aged Mice and Humans
Kiyota N, Zhou Y, Deb DK et al.
bioRxiv : the preprint server for biology · 11 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Important
- Evidence
- Animals
- Status
- Preprint
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