Mouse models of glaucoma and trabecular meshwork dysfunction

Mouse model of Steroid-Induced Glaucoma.

We have developed and validated an animal model of glaucoma which mimics the hallmarks of human Steroid-Induced Glaucoma (SIG) within 4 weeks of systemic Dexamethasone (DEX) treatment. We are currently investigating the pathogenesis of trabecular meshwork dysfunction and ocular hypertension related to SIG. In addition we are using this model to evaluate new ocular therapies aimed at lowering intra-ocular pressure in humans. 

Intra-ocular pressure was elevated by 21% after 4 weeks of DEX treatment (A), and the rate of fluid outflow from the eye was reduced by 56% (B).

Control mice were often observed to have open spaces (stars) between the Juxtacanalicular (JCT) cells with processes extending in many directions, as opposed to the DEX treated JCT often filled with fine fibrillar material (arrows).

In addition, DEX treated mice exhibited accumulations of coiled basement membrane material (arrows) within the JCT and elevated deposition of fine fibrillar sheath material around elastic fibres.

DEX treated mice exhibit a more continuous labelling of type-4 collagen surrounding the inner wall endothelium of the Schlemm’s Canal (arrows).

DEX treated mice have a continuous and dense and compacted basement membrane underlying the inner wall endothelium of Schlemm’s Canal (arrows). In stark contrast to the patchy, openly spaced (stars), basement membrane observed in control mice.

Basement membrane length is significantly longer in DEX treated mice than controls P=0.0003 (B). There was a statistically significant relationship observed between facility and basement membrane length P= 0.001 (C).

Ultrastructural Changes Associated with Dexamethasone-Induced Ocular Hypertensi