Segmental Outflow and Trabecular Meshwork Stiffness in an Ocular Hypertensive Mouse Model

Purpose: Elevated IOP due to increased outflow resistance through the trabecular meshwork (TM) is a major risk factor for POAG. Outflow through the TM is segmental, consisting of high-flow (HF) and low-flow (LF) regions. Here, we investigate how ocular hypertension impacts segmental outflow using a dexamethasone (DEX) mouse model and compare TM stiffness between HF and LF regions. Methods: Nanoparticles containing DEX or vehicle were injected twice weekly in 2- to 4-month-old C57BL/6J mice (n = 14), and the IOP was measured weekly. At week 4, mouse eyes were perfused in vivo with fluorescent nanospheres to assess flow patterns and the circumferential percentage of HF, intermediate-flow, and LF regions in each eye. Sagittal sections were collected from HF and LF regions, and atomic force microscopy was used to measure tissue stiffness. Immunofluorescent labeling was used to compare fibronectin and alpha-smooth muscle actin protein levels. Results: DEX treatment significantly elevated the IOP by an average of 33.3% and altered tracer distribution but not the percentage of HF and LF regions around the circumference. No significant differences in TM stiffness were detected between DEX-treated and control mice, or between HF and LF regions. Increased fibronectin in LF regions of DEX-treated eyes suggested subtle TM structural changes that were not detected by atomic force microscopy. Conclusions: DEX alters segmental flow distribution and may impact cell contractility rather than ECM stiffness to cause IOP elevation in young mice. These findings better characterize the nature of segmental outflow and TM mechanics in this model of steroid-induced glaucoma.