Abstract
Purpose:
ON and OFF pathways are essential components in visual discrimination. In this study, we evaluated the roles of ON and OFF pathways in mediating visual function during development using pathway-specific mutant mice.
Methods:
Nob mice have a null mutation in the Nyx gene that encodes for the protein nyctalopin; this mutation results in lack of visual signal transmission in the retinal ON pathways. Alternatively, Vsx1 knockout (KO) mice have a null mutation in the visual system homeobox gene 1 (Vsx1), which leads to defects in the differentiation and function of most cone OFF bipolar cells and consequently defective OFF pathway signaling. With their respective wild-type controls (WT), C57BL/6 for nob and 129Sv for Vsx1 KO, we followed the development of visual acuity and peak contrast sensitivity weekly from 2 to 8 weeks of age using the virtual optokinetic system.
Results:
Both nob and Vsx1 KO mice had significantly lower visual acuity levels than their WT counterparts early in development (p<0.05), with nob mice having more severe deficits than Vsx1 KO mice. Both nob and Vsx1 KO mice showed improvements in visual acuity thresholds that plateaued at similar thresholds as WT. However, nob mice did not reach WT levels until postnatal week 7, while Vsx1 KO mice were indistinguishable from WT starting at 3 weeks of age. Both nob and Vsx1 KO mice had consistently lower contrast sensitivities than their WT counterparts throughout the study period (p<0.001). Moreover, the spatial frequency that elicited maximal contrast sensitivity differed between the two WT strains (C57BL/6 vs. 129Sv).
Conclusions:
Collectively, our results suggest that having a functional ON or OFF pathway is sufficient for normal visual acuity development by adulthood, but both pathways are necessary for proper contrast sensitivity perception. It would be interesting to determine if the differential effects of ON or OFF pathway defect on visual acuity and contrast sensitivity are due to differences in retinal dopamine content, a key modulator of the optokinetic response.
Keywords: 756 visual development •
502 dopamine •
693 retinal connections, networks, circuitry