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Bhagwat V Alapure, Jennifer J Lentz; Reduced expression and delayed translocation of α-transducin in photoreceptors of a mouse model of Usher syndrome. Invest. Ophthalmol. Vis. Sci. 2018;59(9):995.
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Rod photoreceptor cell (PRC) sensitivity is mediated, in part, by the light-induced movement of phototransduction proteins between photoreceptor cellular compartments. In the dark, α-transducin resides in rod outer segments (OS) and arrestin in inner segments (IS). At a critical light threshold, α-transducin moves from rod OS to IS and the cell body; whereas arrestin moves from IS to OS. This movement is hypothesized to play an important role in protection from light stress. Harmonin, a scaffolding protein encoded by the USH1C gene, is expressed in cochlear hair cells and photoreceptor IS and OS. In the ear, harmonin plays an important role in hair cell development and function through interactions with other proteins and the stereocilia. The function of harmonin in the retina is not known. Mutations in harmonin cause Usher syndrome (Usher), the leading genetic cause of concurrent hearing and vision loss. Mice that contains the USH1C c.216G>A mutation responsible for Type 1 Usher in the Acadian population in Louisiana, USA and Canada, are deaf, and have vestibular and visual dysfunction similar to patients. We hypothesize that harmonin plays a role in the movement of proteins via interactions with the connecting cilia in PRCs, and that Usher mice have reduced light-activated movement of phototranduction proteins. To test this hypothesis, the expression of phototransduction proteins and glial fibrillary acidic protein (GFAP) was measured in Usher and control retinas after exposure to various light intensities.
Dark adapted USH1C c.216G>A knock-in (Usher) and littermate control mice were exposed to dim and bright light. Retinal expression of α-transducin, arrestin, rhodopsin and GFAP was measured using western blot and immunohistochemistry (IHC) techniques.
Western blot and IHC analyses show reduced expression and delayed translocation of α-transducin, respectively, after dim and bright light exposure in Usher PRCs compared with littermate controls. No difference in arrestin was observed. Rhodopsin was mislocalized in Usher PRCs in dark conditions. GFAP expression was increased in both dark and light conditions in Usher retinas compared with littermate controls.
These data suggest that harmonin may play a role in the movement of phototransduction proteins in PRCs and protection from light stress.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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