Progress in understanding glaucoma pathogenesis has been greatly facilitated by establishing robust, simple and repeatable models that recapitulate physiology relevant disease features. More recently, research groups have sought to develop inducible models on a murine platform to capitalize on the many advantages that this widely used laboratory species offers. Further, to exploit rapid developments in imaging and reporter mouse strains, one would want a glaucoma model that retains optical clarity.
To this end, Chan et al. developed hyaluronic acid-based polymers that are fluid at room temperature but cross link when gradually warmed by the higher temperatures inside the anterior chamber. Following careful characterization, a single 1.5 uL injection into the anterior chamber produced significant IOP elevation of 9 mmHg above the fellow control excellent was sustained throughout the four weeks of monitoring. Importantly the success rate was excellent with ~90% of eye exhibiting significant IOP elevation and any attrition was negligible as no adverse effects were noted.
The optical clarity presents an advantage over a number of murine mode, making this work a significant contribution to pre-clinical glaucoma modelling
Using mice in which yellow fluorescent protein is expressed under a thy1 neuronal promoter (Thy1-YFP-G), the authors nicely show a progressive decline in Thy1-YFP cells over the four weeks and thereby longitudinal in-vivo imaging is unimpeded in this model. They also found that IOP elevation led to optic nerve and optic tract damage as evidenced by reduced diffusion anisotropy using diffusion tensor magnetic resonance imaging. Consistent with what would be expected from chronic IOP related injury, the team demonstrate progressive decline (-1%/day) in visual acuity as measured using the optomotor reflex. Functional deficits specific for retinal ganglion cells could were also observable using the electroretinogram.
This novel simple approach produces robust and sustained IOP elevation, and recapitulates progressive neurodegeneration seen in in human glaucoma. Critically, the optical clarity presents an advantage over a number of murine mode, making this work a significant contribution to pre-clinical glaucoma modelling.