Purchase this article with an account.
Christopher Kai-Shun Leung, Yu Yu, Guihua Xu, Sayantan Biswas, Ying Chau; A Novel Glaucoma Model Induced by Intracameral Injection of Cross-Linking Hydrogel. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2087.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
While experimental glaucoma models are pertinent to investigate the mechanism and treatment of optic nerve degeneration, existing models are limited to afford a sustained elevation of IOP with a clear optical media that allow longitudinal examination of the optic nerve. We introduced here a novel glaucoma model induced by intracameral injection of a hydrogel that forms chemical cross-links after injection, and examined the longitudinal profile of RGC loss in this model with in vivo imaging.
1 eye of each of the 15 transgenic Thy-1 GFP mice (the RGC bodies are intrinsically labeled with GFP) was injected intracamerally (targeted at the anterior chamber angle) with 1.0-2.5µl of a mixture of 4% vinysulfonated hyaluronic acid (HA-VS) and 4% thiolated hyaluronic acid (HA-SH) dissolved in PBS. The mixing of HA-VS and HA-SH formed chemical cross-links and the mixture changed from an injectable form to a solidified, optically clear hydrogel in 5-10 minutes. The IOP was measured with Tonolab at baseline and then daily after hydrogel injection for 4 weeks (≥10 weeks for 5 mice). The RGCs were imaged in vivo with CSLO at baseline and then weekly after hydrogel injection.
8 eyes had sustained IOP elevation for ≥4 weeks after a single injection of ≥1.5µl (FIG. 1). The IOP increased from 9.4±0.4mmHg at baseline, to 24.7±10.0mmHg, 22.8±7.9mmHg, 19.4±8.2mmHg, 20.4±9.3mmHg at week 1, 2, 3, and 4, respectively, for the injected eyes, and 9.1±0.9mmHg, 8.9±0.9mmHg, 9.3±0.7mmHg, 8.9±0.9mmHg, and 9.1±1.0mmHg, respectively, for the fellow eyes. 5 eyes had follow-up ≥10 weeks and the IOP at 10 weeks was 15.7±4.7mmHg. 3 eyes developed corneal clouding that precluded in vivo imaging. RGCs progressively decreased to 50.7±10.0%, 45.1±11.2%, 32.9±11.0%, and 25.9±7.3% at week 1, 2, 3, and 4, respectively, and the loss was sectorial (FIG. 2).
The hydrogel injection model affords chronic (≥10 weeks), moderate (20-25mmHg), and consistent IOP elevation with a clear optical media in most injected eyes. To our knowledge, this is the first study showing progressive, sectorial loss of RGCs in glaucoma in vivo. This model would provide a new paradigm for investigation of neurodegeneration and neuroprotection.
This PDF is available to Subscribers Only