Abstract
Abstract: :
Purpose:Usher syndrome 1B is the most common cause of combined deafness and blindness in developed countries. The defective gene encodes for unconventional myosin VIIa, which is expressed in inner hair cells, in photoreceptor cells of the retina, and in the retinal pigment epithelium. These retinal cells play an important role in light perception, and light/dark adaptation processes. Here, we characterize the retinal phenotype of the mariner mutant, a zebrafish with MyoVIIa mutation. Methods:In order to characterize the mariner phenotypes, we examined light and dark adapted mutant larvae at different developmental stages. The morphology of dark and light adapted retinas was assessed by standard histology and electron microscopy. Immunocytochemistry was used to identify distinct types of neurons and to localize myosin VIIa in the zebrafish retina. Furthermore, the optokinetic response (OKR) was used to analyze light adaptation defects, and electroretinogramms (ERGs) were measured to compare mutant and wt retinal functionality. Results:ERGs reveal no differences between mutant and wt larvae. However, OKR recovery takes more time in the dark adaptation phase of the mutants than the OKR recovery of the wt siblings. Morphological and morphometrical analyses show that pigment migration is impaired in mariner mutants during adaptation. Further immunocytochemical studies will show the localization of MyoVIIa in wild type and mariner retinas, and electron microscopical analysis will elucidate morphological alterations that contribute to the mariner phenotype. Additionally, light damage experiments will show whether a light adaptation defect causes increased photoreceptor degeneration in the mariner mutant. Conclusions:These data are consistent with the hypothesis that the primary defect in the visual system of MyoVIIa mutants is due to a defect in light adaptation. Thus, we suggest that the slow progressive blindness in human Usher disease might be caused by light damage due to impaired light adaptation.
Keywords: retinal degenerations: cell biology • retina: distal (photoreceptors, horizontal cells, bipolar cells) • retinal pigment epithelium