Grimsrud, A. O. | bioRxiv Science

bioRxiv2025

Intracameral Puncture Lowers Intraocular Pressure and Triggers an Immune Response in the Conventional Outflow Tract

PurposeIntracameral injection is an effective delivery method for biomedical agents and therapeutics to conventional outflow tract tissues. However, the effect of intracameral injections on intraocular pressure and aqueous dynamics has not been well characterized, warranting further investigation. MethodsWild type 3-5-month-old C57BL/6 mice were subjected to intracameral puncture (ICP, without injection of any material). Following ICP, intraocular pressure (IOP), outflow facility, aqueous production, episcleral vessel diameter, and macrophage densities were measured. ResultsOn day 1, IOP was significantly reduced by 30% (p < 0.0001; n=25) while outflow facility (p = 0.306; n=15) and aqueous production (p = 0.163; n=9) were unchanged. As well, Schlemms canal filtration area was unchanged, however distal vessels were dilated (p < 0.001) at day 1 post ICP. Correspondingly, macrophage density was significantly increased around episcleral vessels (p < 0.0005) at day 1. Macrophage densities in Schlemms canal and trabecular meshwork, while unchanged at day 1, were significantly increased by day 3 (p < 0.0001). ConclusionsCoincident with significantly reduced IOP one day after ICP, there was an influx of macrophages into the distal portion of the conventional outflow tissues and a dilation of episcleral vessels, likely reducing distal outflow resistance. Our study demonstrates the importance of considering the drug delivery method to the eye due to its effects on the immune response and conventional outflow homeostasis.

physiology↗

bioRxiv2025

Resident Tissue Macrophages Govern Intraocular Pressure Homeostasis

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 Schlemms 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.

immunology↗