MechanismsAnimalsPreprint

Macrophage-derived VEGFA maintains eye outflow in mice

Deleting Vegfa in CX3CR1-positive macrophages raised intraocular pressure and reduced aqueous humor outflow facility in nine-month-old mice.

A cross-section of an eye angle showing macrophages, beside three insets showing progressive cell loss from populated to empty, and a small mouse.

bioRxiv3 Oct 2026, 00:19 BST

In mice and human tissue imaging, aging was associated with reduced Schlemm's canal size and increased macrophage accumulation around the canal. Single-cell RNA sequencing of mouse ocular angle tissues showed immunomodulatory transcriptional reprogramming of Schlemm's canal endothelial cells in older mice. Ligand-receptor analysis predicted enhanced macrophage-to-endothelial VEGFA signaling in aged and Tie2-haploinsufficient mice, an independent model of vascular stress.

Deleting Vegfa in CX3CR1-positive macrophages increased intraocular pressure and reduced aqueous humor outflow facility in nine-month-old mice. Tie2 haploinsufficiency recapitulated age-associated niche changes around the canal, while gene therapy boosting TIE2 activity protected wild-type mice against these age-related shifts.

Why it matters

The findings suggest that immune cells in the eye can act as a compensatory buffer to sustain fluid drainage and pressure regulation as vascular structures alter during aging.

Caveats

This study is a preprint that has not yet been peer-reviewed. While structural imaging included human tissues, all functional genetic deletions and gene-therapy interventions were performed in mice.