Chromophore-loaded CRALBP restores rod visual cycle in chromophore-deficient mice

The visual cycle depends on continuous regeneration and trafficking of 11-cis-retinal, and failure of that process underlies a group of inherited retinal diseases marked by night blindness, delayed dark adaptation, and progressive photoreceptor loss. In a recent issue of Molecular Therapy Advances, Kolesnikov et al.1 test whether CRALBP, a native retinaldehyde-binding protein, can be repurposed as an exogenous carrier to bypass defective chromophore production. They show that 9-cis-retinal-loaded wild-type CRALBP and a redox-sensitive A212C:T250C mutant restore rod function in chromophore-deficient Rpe65−/− mice ex vivo and after intravitreal injection in vivo and that the engineered mutant improves photostability of bound 9-cis-retinal in vitro.