Neuro-behavioural analysis of visual ability in a mouse model of glaucoma

The DBA/2J mouse is a model of human pigmentary glaucoma, as it develops elevated intraocular pressure, retinal ganglion cell (RGC) death, optic nerve degeneration and a reduction of retinal thickness. RGC loss in the DBA/2J mouse can be inhibited by human anti-glaucoma medications such as Timolol, which is a beta-blocker that preserves RGC function by reducing aqueous production. We determined that complete loss of visual function occurs between 6 and 12 months of age in DBA/2J mice. These visual deficits caused DBA/2J mice to perform poorly in the Morris water maze (MWM), a visuo-spatial learning and memory task. DBA/2J mice performed better than C57BL/6J mice (a strain of mice that does not develop age-related blindness) at 6 but not at 12, 18 or 24 months of age. Aged DBA/2J mice outperformed C57BL/6J mice in an olfactory discrimination learning and memory task. We propose to evaluate the effect of Timolol, as a protective agent against RGC loss and thus visual function loss in DBA/2J mice. We will examine the effects of Timolol on behavior, retinal anatomy and neural function. In this way we will be able to dissociate age-related visual and cognitive functions and also correlate changes in retinal anatomy (RGC loss) and neural function with changes in visual function. This research is important because it will correlate age-related visual system changes in the retina and brain with changes in visual ability thereby evaluating a treatment strategy not only on its ability to rescue retinal ganglion cell atrophy but also on its potential to restore visual function and alter patterns of neurodegeneration that occur after blindness.