Current clinical therapies target reduction of IOP to retard glaucomatous neurodegeneration ( The AGIS Investigators, 2000 Early Manifest Glaucoma Trial Group et al., 2002 Lichter et al., 2001), but neuroprotectants are critically needed to prevent degeneration of RGCs and ON. The level of intraocular pressure (IOP) is the most common risk factor ( Singh and Shrivastava, 2009). Glaucoma is a neurodegenerative disease characterized by injury to the axons of retinal ganglion cells (RGCs) followed by progressive degeneration of RGC somata and axons within the retina and Wallerian degeneration of the myelinated axons in the optic nerve (ON) ( Quigley, 1993 Quigley et al., 1995 Libby et al., 2005 Howell et al., 2007 Weinreb and Khaw, 2004 Calkins, 2012 Burgoyne, 2011 Nickells et al., 2012 Jonas et al., 2017). Annual direct medical costs to treat this disease in 2 million patients in the United States totaled $2.9 billion ( Varma et al., 2011). Glaucoma is the most common cause of irreversible blindness and will affect more than 100 million individuals between 40 and 80 years of age by 2040 ( Tham et al., 2014). It may be applicable with only minor modifications to a range of animal species in which it will generate stable, robust IOP elevation and significant neurodegeneration that will facilitate selection of neuroprotectants and investigating the pathogenesis of ocular hypertension-induced glaucoma. This simple, inducible and reversible mouse ocular hypertension model shows dynamic changes of visual function that correlate with progressive retinal ganglion cell (RGC) loss and axon degeneration. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. Here, we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. Understanding the molecular mechanism of glaucoma and development of neuroprotectants is significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma.