Purpose. We assayed the optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb(+) (D2-Gpnmb(+)) and C57BL/6J (B6) mouse strains, and compared retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision between D2 and B6 mouse lines. Methods. Intraocular pressure (IOP) measurements, real time PCR and immunohistochemical analysis were used to assess the time course of glaucomatous changes in D2 retinas. Behavioral analyses of optomotor head turning reflex, visible platform Morris water maze and Rotarod measurements were conducted to test vision and vestibulomotor function. Electroretinogram (ERG) measurements were used to assay outer retinal function. The multielectrode array (MEA) technique was employed to characterize RGC spiking and direction selectivity in D2 and B6 retinas. Results. Progressive increase in IOP and loss of Brn3a signals in D2 animals were consistent with glaucoma progression starting after 6 months of age. D2 mice showed no response to visual stimulation that evoked robust optomotor responses in B6 mice at any ages after eye opening. Spatial frequency threshold was also not measurable in the D2-Gpnmb(+) strain control. ERG a- and b-waves, central vision, vestibulomotor function, the spiking properties of ON, OFF, ON-OFF and direction-selective RGCs were normal in young D2 mice. Conclusions. The D2 strain is characterized by a lack of optomotor reflex before IOP elevation and RGC degeneration are observed. This behavioral deficit is D2 strain-specific but independent of retinal function and glaucoma. Caution is advised when using the optomotor reflex to follow glaucoma progression in D2 mice.