| Abstract No.: | A-D1128 |
| Country: | Canada |
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| Title: | AGE-RELATED CHANGES IN VISUAL ABILITY AND COGNITIVE FUNCTION IN THE DBA/2J MOUSE MODEL OF GLAUCOMA |
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| Authors/Affiliations: | 1 Aimee Wong*; 1 Richard Brown;
1 Dalhousie University, Halifax, NS, Canada
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| Content: | Objectives: The DBA/2J mouse is used as a model of human pigmentary glaucoma as it shows age-related increases in intraocular pressure, retinal ganglion cell death and visual impairment (Moon 2005, Cell Tis Res, 320, 51). Visual ability as measured by performance in a visual detection, pattern discrimination and visual acuity test declines from 9 -12 months of age, after which time these mice are functionally blind (Wong & Brown 2007, Neurobiol Aging, 28, 1577). Visual impairment is correlated with poor performance in visuo-spatial tasks, such as the Morris water maze but not in non-visually dependent tasks such as an olfactory learning and memory task and the Rotarod (Brown & Wong 2007, Learn Mem. 13, 134). The purpose of this experiment is to evaluate the effect of a conventional anti-glaucoma medication used in humans, Timoptic-XE, as a protective agent against retinal ganglion cell loss and thus visual function loss. We hypothesize that DBA/2J mice receiving Timoptic-XE will show a dose-dependent improvement in the behavioral visual assessments and should show no deficits in visuo-spatial learning and memory tasks. Furthermore, changes in visual acuity with age should correlate with performance in the Morris water maze, as this task relies on visual information but there should be no effect of changes in vision in the olfactory discrimination learning and memory task, which does not rely on vision.
Materials and Methods: We treated DBA/2J mice with a conventional anti-glaucoma medication used in humans, Timoptic-XE, which is a beta-blocker that decreases intraocular pressure, thus preventing retinal ganglion cell death. Mice were given Timoptic-XE (0.0, 0.25 or 0.5%) in the form of eye drops daily from 2.2 - 12 months of age. At 3, 6, 9 and 12 months of age, mice were tested in a visual detection, pattern discrimination and visual acuity task using the visual water box. Mice were also tested in two learning and memory tasks, the Morris water maze and an olfactory discrimination learning and memory task at each age.
Results: At all ages tested (3, 6, 9 and 12 months of age), mice treated with Timoptic-XE (0.25 and 0.5%) maintained a high level of performance in all tasks, while 12 month old control mice (0%) exhibited impaired performance in visually-dependent, but not non-visual tasks.
Conclusion: These results further validate the DBA/2J mouse model of pigmentary glaucoma as these mice respond to the same treatment as humans with glaucoma. Furthermore, these results demonstrate that when sensory function is preserved in these mice, cognitive function is normalized. Thus, mouse models of cognitive dysfunction must be examined to ensure that behavioral performance is not confounded by sensory dysfunction.
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