Figure 6. ERG in Rs1-KO mice showing that AAV8scRS/IRBP-hRS1 gene transfer improves synaptic function.
(A) Representative ERG waveforms (n = 3) from the treated and untreated eyes of an Rs1-KO mouse that received a unilateral injection of AAV8-scRS/IRBP-hRS1 (2.5 × 109 vg/eye) at P30 compared with responses from a WT mouse. The dark-adapted ERG b-wave amplitude recorded from the untreated eye at P90 is decreased relative to the a-wave amplitude when compared with WT, indicating a reduced postsynaptic BC response to photoreceptor signaling. The AAV8scRS/IRBP-hRS1–treated eye, however, shows a selective improvement in b-wave amplitude, resulting in a waveform more similar to that of the WT. This indicates a restoration of postsynaptic responses. The a-wave amplitude is measured from baseline (0 ms) to the negative trough; b-wave amplitude is measured from the a-wave trough to the positive peak. Stimulus flash occurs at 0 ms. Arrows indicate the a-wave implicit time (time from stimulus flash to peak amplitude) for the treated and untreated eyes. (B) The a-wave implicit time for mice injected in 1 eye with 1 μl of AAV8-RS1 at various doses or with 1 μl of vehicle. Values represent the average difference between the untreated and treated eyes (untreated – treated) at each dose. The a-wave implicit time is significantly shorter in treated eyes at doses of 1.0 × 108 vg/eye and higher. Asterisks indicate significance compared with zero, the value expected if there is no effect of treatment (*P < 0.05; ****P < 0.0001, 1-sample t test). n = 4.