FIG. 4.

RHO301–siRNA301 gene transfer rescued retinal function in P23H transgenic mice. (A) a-wave amplitudes were measured 1, 2, 3, 6, and 9 months postinjection. The data presented here are from high-intensity flashes (0 dB) and represent both rod and cone responses. AAV-RS301-injected eyes exhibited a significantly increased a-wave response at all time points compared with control injected eyes (AAV-GFP) (n=9, **p<0.005 at 1, 3, 6, and 9 months; p<0.05 at 2 months). (B) b-wave amplitudes are presented from 1, 2, 3, 6, and 9 months postinjection. Right AAV-RS301-injected eyes showed a significantly increased b-wave response compared with left AAV5-GFP-treated eyes (n=9 at 1, 2, 6, 9 months; **p<0.005 at 3 months, *p<0.05). To determine the extent of rescue of ERG amplitudes in P23H eyes relative to untreated wild-type eyes, we compared a-wave and b-wave amplitudes in P23H transgenic mice with those of nontransgenic mice at 1 month postinjection (C) and 9 months postinjection (D). Left eyes of both strains were untreated and right eyes were injected with AAV-RS301. ERG amplitudes of the untreated nontransgenic eyes were set at 100% for both time points. At 1 month, both the uninjected transgenic and injected nontransgenic eyes showed a statistically significant (*p<0.05) decrease in a-wave amplitude. However, by 9 months only the untreated P23H transgenic eyes showed a significantly diminished response in both a- and b-wave amplitudes,<20% that of the untreated, nontransgenic eyes (n=7; **p<0.005). P23H eyes injected with AAV-RS301 maintained 80% of the a-wave amplitude of untreated nontransgenic eyes (p>0.05). For the b wave, P23H eyes injected with AAV-RS301 maintained almost 95% of the amplitude of the uninjected, nontransgenic eyes.