Development and Characterization of Silicone Oil-Induced Reversible Ocular Hypertension Glaucoma Model

Stanford University, Stanford CA

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Abstract

PROJECT SUMMARY Glaucoma is the most common cause of irreversible blindness due to the death of retinal ganglion cells (RGCs) and degeneration of optic nerve (ON). Neuroprotectants that promote RGC survival, stem cell-derived RGCs to replace lost RGCs after transplantation and regeneration therapies to stimulate RGC soma and axon regeneration are promising neural repair strategies for vision restoration in glaucoma patients. A relevant translation-enabling animal glaucoma model is critical, but the current available ocular hypertension models, such as laser photocoagulation caused trabecular meshwork (TM) impairment and microbead occultation of TM, are technically challenging and often involved multiple treatments with unstable IOP elevation and irreversible ocular tissue damage. It is crucially important and in urgent need to develop a simple, reliable, and more importantly, reversible experimental ocular hypertension/glaucoma model in the animal species that closely resembles human glaucoma, such as nonhuman primate (NHP). To take on this challenge, we recently developed and characterized a simple procedure of intracameral injection of silicone oil (SO) in mouse eyes that blocks the pupil, causes accumulation of aqueous humor in the posterior chamber and induces ocular hypertension, which can be removed to lower IOP to normal and faithfully replicates post-operative secondary glaucoma in human patients. NHP's visual system closely resembles human anatomy, especially has macula and lamina cribrosa that do not present in mouse. NHP glaucoma model is most likely to predict human responses to ocular hypertension and therapies. We propose to extend our successful mouse SO-induced reversible ocular hypertension model into a novel NHP glaucoma model, success of which will enable us for the first time to test neuroprotective and regenerative strategies together with IOP lowering situation that faithfully mimic clinical scenarios in the closest animal species to human.