Usher syndrome combines congenital hearing loss and retinitis pigmentosa (RP). Mutations in the whirlin gene (DFNB31/WHRN) cause a subtype of Usher syndrome (USH2D). Whirler mice have a defective whirlin gene. They have inner ear defects but usually do not develop retinal degeneration. Here we report that, in whirler mouse photoreceptors, the light-activated rod transducin translocation is delayed and its activation threshold is shifted to a higher level. Rhodopsin mis-localization is observed in rod inner segments. Continuous moderate light exposure can induce significant rod photoreceptor degeneration. Whirler mice reared under a 1500 lux light/dark cycle also develop severe photoreceptor degeneration. Previously, we have reported that shaker1 mice, a USH1B model, show moderate light-induced photoreceptor degeneration with delayed transducin translocation. Here, we further show that, in both whirler and shaker1 mice, short-term moderate light/dark changes can induce rod degeneration as severe as that induced by continuous light exposure. The results from shaker1 and whirler mice suggest that defective transducin translocation may be functionally related to light-induced degeneration, and these two symptoms may be caused by defects in Usher protein function in rods. Furthermore, these results indicate that both Usher syndrome mouse models possess a light-induced retinal phenotype and may share a closely related pathobiological mechanism.

This work aimed to investigate benzophenanthridine from the roots of Zanthoxylum nitidum (Roxb.) DC. var. fastuosum How ex Huang for the first time. Thirteen benzophenanthridines were isolated, and our results of the cytotoxic activities indicated that compound 6 exhibited the best potency against A549, Hela, SMMC-7721 and EJ, with the IC50 values of 27.50, 37.50, 16.95 and 60.42 μM, respectively. Compounds 7 and 11 also showed strong cytotoxicity when tested against the four human cancer cell lines (A549, Hela, SMMC-7721 and EJ), while only compounds 12 and 13 displayed cytotoxicity in inhibiting BALL-1 proliferation among all the compounds. These results suggested that benzophenanthridines may become a valid alternative of potential basis for new anti-proliferative agents.