At P14,
rd10 mice were subretinally injected with AAV5-smCBA-PDEβ. Three weeks after treatment (1 week after removal of mice to a cyclic light environment),
rd10 mice were examined by dark-adapted and light-adapted electroretinography. Larger dark- and light-adapted ERG responses were evident in vector-treated eyes. When the stimulus intensity was 2.68 cd · s/m
2, the average dark-adapted ERG b-wave amplitudes in PDEβ treated
rd10 eyes were 200 ± 20 μV (
Fig. 2A ;
n = 3), which was 37% of the isogenic wild-type mice (544 ± 89 μV;
n = 3) and approximately threefold higher than in contralateral untreated eyes (70 ± 40 μV;
n = 3). Paired
t-test analysis showed significantly smaller dark-adapted b-wave amplitudes in untreated
rd10 eyes compared with C57 eyes (
P < 0.01). Although statistically not as good as those in normal C57 eyes (
P < 0.05), dark-adapted b-wave amplitudes were significantly improved in treated
rd10 eyes compared with those in untreated
rd10 eyes (
P < 0.05). Light-adapted ERG b-wave amplitudes elicited with a flash intensity of 12 cd · s/m
2 were 118 ± 25 μV in normal, 109 ± 23 μV in treated
rd10, and 66 ± 29 μV in untreated
rd10 eyes
(Fig. 2B) . Statistical analysis showed similar light-adapted ERG b-wave amplitudes (
P = 0.6) between normal C57 and treated
rd10 eyes 3 weeks after injection (
n = 6), whereas a significant difference was found between treated and untreated
rd10 eyes (
P < 0.05;
n = 6).
Figure 2C 2Dshows a representative
rd10 mouse 5 weeks after one eye received subretinal vector at P14 (P49, 3 weeks after returning to cyclic light environment). In the untreated
rd10 eye, dark-adapted ERG responses were minimal
(Fig. 2C) , whereas the light-adapted b-wave amplitudes
(Fig. 2D)were approximately 25% of the wild-type controls elicited with flash intensity of 12 cd · s/m
2. In the treated
rd10 eye, approximately 22% of the normal dark-adapted b-wave
(Fig. 2C)and 82% of the normal light-adapted b-wave amplitudes elicited with flash intensity of 2.68 cd · s/m
2 (Fig. 2D)persisted. In time domain, the implicit times of the dark- and light-adapted ERG b-waves were approximately 75 ms (2.68 cd · s/m
2) and 45 ms (12 cd · s/m
2), respectively. In the treated
rd10 mouse eye, the implicit time of the dark-adapted b-wave was comparable to that of the wild type mouse; however, the implicit time of the light-adapted b-wave was approximately 60 ms, which is similar to that for the untreated eye but is approximately 15 ms longer than for the normal control. Finally, as additional controls, we tested subretinal AAV5-smCBA-GFP and PBS in
rd10 eyes. No rescue effects were observed in these eyes, indicating rescue is not a consequence of the injection procedure itself (data not shown).