Disease mechanisms revealed in the P23H opsin knock-in mouse model of retinitis pigmentosa

-acetylcysteine (NAC) exhibited higher intensities of SW-AF, improved photoreceptor viability, and diminished 4-hydroxynonenal (HNE) immunoreactivity; the latter included 4-HNE adducts deposited in association with photoreceptor cells. The lower levels of bisretinoid in association with higher retinal illuminance are indicative of toxic bisretinoid photooxidation/degradation while the higher bisretinoid levels conferred by NAC are consistent with inhibition of these photodegradative processes. Collectively, these findings reveal that anomalous bisretinoid production can account for fundus hyperautofluorescence, and the photoreactive properties of bisretinoids can explain the propensity for environmental light to exacerbate photoreceptor cell degeneration. The findings support the benefits of antioxidant intervention in human adRP.