A Robust Microbead Occlusion Model of Glaucoma for the Common Marmoset

Abstract

Purpose: To establish a robust experimental model of glaucoma in the common marmoset (Callithrix jacchus), a New World primate, using an intracameral microbead injection technique. Methods: Elevated intraocular pressure (IOP) was induced by an injection of polystyrene microbeads. Morphologic changes in the retina and optic nerve of glaucomatous eyes were assessed and electroretinogram (ERG) recordings were performed to evaluate functional changes. Results: Microbead injections induced a sustained IOP elevation for at least 10 weeks in a reproducible manner. At the end of the 10-week experimental period, there was significant loss of retinal ganglion cells (RGCs) in all quadrants and eccentricities, although it was more prominent in the mid-peripheral and peripheral regions. This was consistent with a thinning of the Retinal nerve fiber layer (RNFL) seen in spectral domain optical coherence tomography scans. Surviving RGCs showed marked changes in morphology, including somatic shrinkage and dendritic atrophy. Retinas also showed significant gliosis. The amplitude of the ERG photopic negative response, with subsequent a-and b-wave changes, was reduced in glaucomatous eyes. The optic nerve of glaucomatous eyes showed expanded cupping, disorganization of the astrocytic matrix, axonal loss, and gliosis. Conclusions: We developed a robust and reproducible model of glaucoma in the marmoset. The model exhibits both structural and functional alterations of retina and optic nerve characteristic of glaucoma in humans and animal models. Translational Relevance: The glaucoma model in the marmoset described here forms a robust method to study the disease etiology, progression, and potential therapies in a nonhuman primate, allowing for more effective translation of animal data to humans.