Abstract
Purpose :
Glaucoma is one of the most prevalent causes of world blindness, characterised by high IOP and associated loss of retinal ganglion cells in the retina. For the development of novel therapies, reliable animal models that mimic disease pathology are still lacking and improvements to current models, as well as understanding of differences amongst strains are also needed.
Methods :
An experimental model of glaucoma induced by injection of magnetic microspheres into the anterior chamber to increase intraocular pressure (IOP) was examined for phenotypic and electrophysiological responses in two rat strains. We injected spheres at various concentrations (20, 15, 10, or 5mg/ml) using Lister Hooded or Norway Brown rats. IOP was measured for up to a period of 7 weeks using a rebound tonometer. Optic nerve damage was determined by electron-microscopy examination and retinal ganglion cell function was assessed by measurement of the scotopic negative and positive threshold responses of the ERG.
Results :
There was a significant rise in IOP and decline in RGC function and number, for Norway brown rats receiving 20, 15 or 10mg/ml microspheres. The results showed that 10mg/ml microspheres are optimal to produce a rise in IOP that was related to the functional damage in RGCs as shown by significant impairment to the nSTR and pSTR. However, Lister hooded did not respond as robustly to the microbeads, showing higher variability in IOP. An impairment to the pSTR and nSTR was observed in Lister hooded rats, independent of IOP elevation. There were no significant differences in ERG responses of the control eyes between the strains. Electron microscopy analysis of the axonal damage showed a significant impairment of RGC axons in both strains.
Conclusions :
This magnetic microsphere model is easy to conduct and appears to resemble human disease when induced in the Norway brown rat. This is suggested by observations that raised IOP correlates to RGC loss and associated functional decline. However, this response is not replicated in the Lister hooded strain. Further investigations on the physiological and anatomical differences between strains may aid in the selection of animals for experimental studies of glaucoma therapies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.