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Abstract #125356 Published in IGR 25-2
Resident Tissue Macrophages Govern Intraocular Pressure Homeostasis
Liu KC; Grimsrud AO; Suarez MF; Suarez MF; Schuman D; De Ieso ML; De Ieso ML; Kuhn M; Kelly RA; Mathew R; Kalnitsky J; Mack M; Ginhoux F; Bupp-Chickering V; Bupp-Chickering V; Balasubramanian R; John SWM; Stamer WD; Saban DRbioRxiv : the preprint server for biology 2025; 0:
Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of the optic nerve, or glaucoma. Although macrophages reside throughout the conventional outflow tract, their role in regulating intraocular pressure remains unknown. Using macrophage lineage tracing approaches, we uncovered a dual macrophage ontogeny with distinct spatial organizations across the mouse lifespan. Long-lived, resident tissue macrophages concentrated in the trabecular meshwork and Schlemm's canal, whereas short-lived monocyte-derived macrophages, instead, were abundant around distal vessels. Specific depletion of resident tissue macrophages triggered elevated intraocular pressure and outflow resistance, linked to aberrant extracellular matrix turnover in the resistance-generating tissues of the trabecular meshwork. This dysregulated physiology and tissue remodeling were not observed when we depleted monocyte-derived macrophages. RESULTS: show ontogeny and tissue-specific macrophage function within the outflow tract, uncovering the integral homeostatic role of resident tissue macrophages in resistance-generating tissues whose dysfunction is responsible for glaucoma.
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