Abstract
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. 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. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. 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. 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.
Highlights
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)
Intravitreal injection of silicone oil (SO) in vitreoretinal surgeries can cause post-operative secondary glaucoma in humans (Ichhpujani et al, 2009; Kornmann and Gedde, 2016), we reasoned that direct injection of SO into the anterior chamber of mice would be more efficient, preventing the need to remove the vitreous and reducing toxicity due to direct contact with the retina
We developed a highly effective and reproducible method adopted from a clinical secondary glaucoma complication after retina surgery
Summary
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). Annual direct medical costs to treat this disease in 2 million patients in the United States totaled $2.9 billion (Varma et al, 2011). The level of intraocular pressure (IOP) is the most common risk factor (Singh and Shrivastava, 2009). 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. Similar to other chronic neurodegenerative diseases (Varma et al, 2008), the search for neuroprotectants to treat glaucoma continues. To longitudinally assess the molecular mechanisms of glaucomatous degeneration and the efficacy of
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