A novel inducible and reversible mouse glaucoma model: Silicone Oil-Induced Ocular Hypertension Under-detected (SOHU)

Abstract

Purpose : Understanding of the molecular mechanism of glaucomatous degeneration and development of neuroprotectants are significantly hindered by the lack of a reliable animal glaucoma model that can be easily reproduced. Elevated intraocular pressure is the most recognized risk factor for glaucoma. We resolved to develop a mouse ocular hypertension model that more closely than available models mimics secondary glaucoma observed in Eye clinic.

Methods : The post-operative secondary glaucoma caused by the silicone oil (SO) used in vitreoretinal surgeries motivated us to test a simple procedure for intracameral injection of SO in mouse eye. Following this injection SO forms a bubble on the surface of iris in the anterior chamber that seals the pupil and prevents influx of aqueous humor into the anterior chamber. We characterized this mouse model in detail at different time points after SO injection with in vivo analysis of RGC function by pattern ERG (PERG) and optokinetic response (OKR), and of structural RGC changes by OCT; and definitive post-mortem histological quantification of surviving RGC somata and axons. Each treatment group contained 8-12 mice.

Results : Mouse eyes injected with SO consistently developed ocular hypertension (20-30 mmHg, about two folds higher than contralateral normal control eyes) due to pupillary blocking that remained stable for at least 8 weeks. The IOP elevation could only be accurately measured after pupil dialysis, which allows aqueous humor to bypass SO and flow into anterior chamber. We thus named this novel experimental glaucoma model “silicone oil ocular hypertension under-detected (SOHU)”. SOHU is a reversible glaucoma model because once we removed SO from the mouse eye, the IOP level quickly returned to normal. Dynamic changes of PERG amplitudes and thinning of the ganglion cell complex detected by OCT imaging correlate with progressive RGC somata loss in retina and axon degeneration in optic nerve.

Conclusions : We found that this simple, inducible and reversible mouse SOHU model with significant neurodegeneration faithfully replicates the secondary glaucoma that is commonly observed in Eye clinic. We believe the SOHU model can be easily adapted to other experimental animal species to study pathogenetic mechanisms and selection of neuroprotectants.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.