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Abstract #47053 Published in IGR 13-3
Timoptic-XE prevents retinal, neural and behavioural signs of visual impairment in the DBA/2J mouse model of glaucoma
Wong AA; Brown REGenes, Brain and Behavior 2010; 9: 439-440
The DBA/2J mouse is used as a model of human pigmentary glaucoma because it shows age-related increases in intraocular pressure (IOP), retinal ganglion cell (RGC) death and visual impairment (Moon 2005, Cell Tis Res, 320, 51; Wong & Brown 2007, Neurobiol Aging, 28, 1577). We evaluated the effect of Timoptic-XE, a conventional glaucoma medication used in humans, on behaviour, IOP, retinal ganglion cell death and transneural labelling in aging DBA/2J mice. Mice were given Timoptic-XE (0, 0.25 or 0.5%) 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 and their learning and memory ability was evaluated using the Morris water maze and a conditioned odor preference task. IOP of all mice was measured after each battery of behavioural tests. At each age, a subgroup of mice from each drug group were given intraocular injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) to visualize and quantify the strength of the connections from the retina to the superior colliculus and a subset of tissue sections were Nissl stained to evaluate somatal size and cell count in the superior colliculus. Retinal flat mounts from these mice were Nissl stained to evaluate retinal ganglion cell number. At all ages tested, mice treated with Timoptic-XE (0.25 and 0.5%) maintained a high level of performance in all behavioural tasks, while 12 month old control mice (0%) exhibited impaired performance in visually-dependent, but not non-visual tasks. Mice treated with Timoptic-XE also maintained significantly lower intraocular pressure from 6-12 months of age and had a significantly higher retinal ganglion cell count than mice treated with 0.0% Timoptic-XE at 12 months of age. Behavioural assessments were correlated with IOP, RGC loss, transneural labeling and cell count in the superior colliculus. These results further validate the usefulness of the DBA/2J mouse model of pigmentary glaucoma as these mice respond to the same treatment as humans. Furthermore, this study provides evidence for the nullsensory impairment hypothesisnull of aging by showing that DBA/2J mice with improved vision can learn visuo-spatial tasks, demonstrating that their impairment is sensory rather than cognitive and that repairing the sensory deficit facilitates improvement in cognitive function.
A.A. Wong. Psychology Department, Neuroscience Institute, Dalhousie University, Halifax, Canada.
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
