Molecular and Histological Characterization of a Novel Hydrogel-Based Strategy for Inducing Experimental Glaucoma in Mice.

Glaucoma is a leading cause of irreversible blindness, and animal models are essential for studying its pathophysiology and testing therapeutic strategies. In this study, a novel hydrogel-based approach was developed and evaluated to induce experimental glaucoma in mice, using composites of hyaluronic acid (HA) and the self-assembling peptide fluorenylmethoxycarbonyl-diphenylalanine (FmocFF). Two formulations with different HA-to-FmocFF ratios were injected either intracamerally or intravitreally in C57BL/6 mice. Intraocular pressure (IOP) was monitored over 21 days, and retinal tissues were analyzed histologically and immunohistochemically. Significant IOP elevation was observed in one hydrogel formulation (Mixture B), yet without detectable retinal ganglion cell loss. A significant reduction in retinal ganglion cell (RGC) density, independent of IOP changes or injection site, was observed in Mixture A. Histological staining confirmed successful delivery and localization of the hydrogel in the anterior chamber, and no evidence of gliosis, microglial activation, or increased apoptosis was revealed by immunostaining. Collectively, these data position the HA-FmocFF hydrogel as a proof-of-concept that advances glaucoma model development, although it does not yet recapitulate the full disease. This model may facilitate future studies of neuroprotection and disease-modifying therapies in glaucoma without confounding inflammatory responses.