Reviewing, in 1999, the non-genetic factors that regulate retinal degeneration, we (Stone et al., 1999) hypothesized that the loss of vision during degeneration results only partly from photoreceptor death. Significant visual loss results, we argued, from loss of performance in surviving photoreceptors, and might be reversible. To test the idea, we first demonstrated that, in the rhodopsin-mutant P23H-3 transgenic rat, the retina is hypersensitive to modest levels of ambient light, which accelerate photoreceptor death, shorten outer segments and degrade the ERG more severely than in non-degenerative controls (Walsh et al., 2004). A comparable hypersensitivity to ambient light has since been reported in a rhodopsin-mutant degeneration which occurs naturally in the dog (Cideciyan et al., 2005).