Detection of visual deficits in aging DBA/2J mice by two behavioral assays

The DBA/2J mice have been used as an animal model for human pigmentary glaucoma. However, these mice develop various degrees of disease symptoms at different ages, making it difficult to detect pathological changes of retinal degeneration at glaucoma onset. The purpose of this study is to develop a non-invasive assay to identify individual mice that develop visual deficits.

We apply two behavioral tests, a swimming test of visual discrimination and a test of optomotor response, to identify glaucomatous DBA/2J mice. We then examine whether the elevation of intraocular pressure (IOP), the common risk factor for glaucoma, affects visual performances of the DBA/2J mice. We further compare the retinal ganglion cell death, one of the signature glaucoma symptoms, in mice with normal behavior with those with poor visual performances.

Our data demonstrate that (1) the onset of visual deficits in DBA/2J mice is around 7 months of age; (2) within each age group, there are various degrees of visual deficits; and (3) the percentage of mice exhibiting visual deficits increases with age and their visual capacities decrease gradually. Furthermore, the poor visual performances of DBA/2J mice do not correlate with the elevation of IOP. Importantly, compared to mice with normal visual performances in the same age group, mice with poor visual performances exhibit significant loss of retinal ganglion cells.

Our studies establish a reliable behavioral assay to identify glaucomatous DBA/2J mice, thus making it possible to examine subtle pathological changes and molecular mechanisms in glaucoma pathogenesis with a relatively small number of samples.