A neurobehavioral analysis of the prevention of visual impairment in the DBA/2J mouse model of glaucoma

Purpose. Timoptic-XE treatment was used to examine the relationship between age-related changes in intraocular pressure (IOP), retinal cell loss, visual ability, and neuronal labeling in the superior colliculus in the DBA/2J mouse model of pigmentary glaucoma. Methods. Mice were administered Timoptic-XE (0.0%, 0.25%, or 0.50%) daily from 9 weeks to 12 months of age. Visual ability and IOP were evaluated at 3, 6, 9, and 12 months of age. Mice from each group were then given intraocular injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), and estimates of the number of cells in the ganglion cell layer of the retina, WGA-HRP transneural labeling of cells, cell count, and cross-sectional area of Nissl-stained cells in the superior colliculus were obtained. Results. Mice treated with 0.50% and 0.25% Timoptic-XE maintained a high level of performance in behavioral vision tasks, while 12-month-old untreated mice (0.0% Timoptic-XE) exhibited impaired visual performance. Timoptic-XE therapy reduced IOP and cell loss in the ganglion cell layer of the retina and prevented somal shrinkage and the decrease in WGA-HRP transneural labeling in the superior colliculus that occurred in untreated mice at 12 months of age. Conclusions. This study provides a comprehensive assessment of the efficacy of Timoptic-XE in DBA/2J mice by correlating age-related visual system changes in the retina and brain with changes in IOP and visual ability. These results showed that reducing IOP not only rescued retinal ganglion cell atrophy but also restored visual function and altered patterns of neurodegeneration that occur with blindness.