Effect of Ret-NH₂ on mouse cone dark adaptation. (A and B) Cone b-wave ERG responses were recorded in vivo (A), and cone a-wave ERG responses were recorded ex vivo (B). Sensitivity in each case was estimated as the ratio of the dim flash response and the corresponding flash intensity and further normalized to the maximal ERG response amplitude. Rod transducin α-deficient mice (Gnat1^−/−) were used to isolate the cone-specific component of the light responses. Mice (3 mo old) were dark adapted overnight, injected with 50 µl DMSO or Ret-NH₂ dissolved in DMSO to 5 µg/µl, and then kept in darkness for 22–26 h. After determining the sensitivity in the dark-adapted state, we exposed the eyes or isolated retinas for 30 s to bright 520-nm light estimated to bleach >90% of their visual pigment. Episodic dim flash stimulation was then used to follow the recovery of cone b-wave sensitivity in vivo (A) in mice treated with DMSO (n = 16) or with Ret-NH₂ (n = 10). Ret-NH₂ did not affect the early phase of cone dark adaptation driven by the intraretinal visual cycle but blocked its late phase, driven by the RPE visual cycle. Recovery of cone a-wave sensitivity ex vivo (B) was measured in isolated retinas from mice treated with DMSO (n = 7) or with Ret-NH₂ (n = 6). Ret-NH₂ did not affect the dark adaptation of cones in isolated retina. Data are presented as means ± SEM.