Fig. 5.

LiGluR expression restores innate and learned light-guided behavior in rd1 mice in vivo. (A) Schematic showing the light/dark box for the open field test. (B) Percentage of time spent in the dark compartment plotted before (black) and after (gray) administration of MAG0₄₆₀ for rd1 RGC-LiGluR (n = 18), rd1 ON-BC–LiGluR (n = 13), and wt mice (n = 4). Data are mean ± SEM. **P < 0.005, ***P < 0.0005; paired Student t test (light intensity: 7 mW/cm² or 1.6 × 10¹⁶ photons per cm⁻²⋅s⁻¹). (C) Biological t_1/2 of intravitreally injected MAG0₄₆₀. RGC-LiGluR–expressing rd1 mice were injected with a single dose of MAG0₄₆₀ in vivo 24 h before day 1. Subsequently, on days 2–14, retinal explants were prepared and responses to 3-s flashes were plotted. The decay of LiGluR-MAG0₄₆₀–induced light responses was fit with an exponential curve decay constant τ = 8.75 ± 0.79 d. (D) Efficacy of MAG over time in vivo. RGC-LiGluR–expressing rd1 mice (n = 7) from B were tested over the course of 10 d. The percentage of time spent in the dark compartment is plotted for rd1 RGC-LiGluR mice before MAG0₄₆₀ (n = 18) and for rd1 RGC-LiGluR mice after receiving a single intravitreal dose of MAG0₄₆₀ at day 2 (n = 18), day 4 (n = 7), day 6 (n = 7), day 8 (n = 7), and day 10 (n = 7). Data are mean ± SEM. *P < 0.01, ***P < 0.0001; multiple t tests with Bonferroni correction. (E and F) Forced two-choice associative learning task with a modified radial arm maze. (E) Schematic of the maze with dimensions given in centimeters. (F) Performance of the four groups of mice on day 1 (black) vs. day 8 (gray). Percentage of correct choices is plotted for sham (PBS)-treated rd1 mice [−LigluR, −MAG0₄₆₀ (n = 8); rd1 RGC-LiGluR + MAG0₄₆₀ (n = 9); rd1 ON-BC–LiGluR + MAG0₄₆₀ (n = 6); and wt mice (n = 6)]. Data are mean ± SEM. *P < 0.05, **P < 0.005, paired Student t test (light intensity at the divider 5 mW/cm² or 1.1 × 10¹⁶ photons per cm⁻²⋅s⁻¹).