Retinal ganglion cell degeneration in a rat magnetic bead model of ocular hypertensive glaucoma

Abstract

Purpose: Glaucoma remains a leading cause of irreversible blindness worldwide. Animal glaucoma models replicate high intraocular pressure, a risk factor for glaucoma, to induce retinal ganglion cell (RGC) degeneration. We describe an inducible, magnetic bead model in the Brown Norway rat in which we are able to determine degeneration across multiple RGC compartments at a time point that is appropriate for investigating neurodegenerative events and potential treatment effects. Methods: We induced ocular hypertension through injection of magnetic microspheres into the anterior chamber of Brown Norway rats; un-operated (naïve) rats served as controls. Intraocular pressure was recorded, and eye diameter measurements were taken before surgery and at the terminal end points. We assessed RGC degeneration and vascular changes through immunofluorescence, and axon transport to terminal brain thalami through intravitreal injection of fluorophore-conjugated cholera toxin subunit β. Results: We observed clinically relevant features of disease accompanying RGC cell somal, axonal, and dendritic loss. RGC axonal dysfunction persisted along the trajectory of the cell into the terminal brain thalami, with clear disruption at the optic nerve head. We also observed vascular compromise consistent with human disease, as well as an expansion of global eye size with ocular hypertension. Conclusions: The magnetic bead model in the Brown Norway rat recapitulates many clinically relevant disease features of human glaucoma, including degeneration across multiple RGC compartments. Eye expansion is likely a result of rodent scleral elasticity, and we caution that this should be considered when assessing retinal density measure-ments. Translational Relevance: This model offers a disease-relevant platform that will allow for assessment of glaucoma-relevant therapeutics.