Intracameral Injection of a Photocrosslinkable Methacrylated Hyaluronic Acid Hydrogel to Establish a Mouse Model of Chronic Ocular Hypertension

Background/Objectives: Chronic ocular hypertension (COH) models are essential for glaucoma research. In this study, we established a mouse COH model by in situ photocrosslinking of methacrylated hyaluronic acid (MAHA). Methods: A 2% (w/v) MAHA precursor containing the photoinitiator LAP was injected into the anterior chamber of C57BL/6J mice and crosslinked under 405 nm light to obstruct aqueous outflow. Hydrogel properties, cytocompatibility, intraocular pressure (IOP), Brn3a retinal flat mounts, flash visual evoked potentials (FVEPs), and serum cytokines were assessed; sham-operated and irradiation-only pilot controls were included. Results: The precursor gelled within 30 s (storage modulus ~4100 Pa), lost <10% mass over 28 days, and showed >97% cell viability. IOP rose from 11.5 ± 0.20 mmHg at baseline to a peak of 24.40 ± 0.67 mmHg (day 12) and remained elevated for 28 days (success rate 60%; failures were surgical complications). Retinal ganglion cell (RGC) loss was ~17% at day 14 and 24–31% at day 28; FVEP P2 amplitude decreased by ~50% with ~30% longer latency; and serum cytokines were unchanged. Pilot controls showed no IOP elevation or RGC loss. Conclusions: A single intracameral MAHA injection induces sustained ocular hypertension with progressive RGC loss and visual pathway dysfunction, without acute ischemic injury, providing a practical model for glaucoma research and neuroprotective drug screening.