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Lucia Ziccardi, Camasamudram Vijayasarathy, Robert N. Fariss, Maria M. Campos, Ronald A. Bush, Paul A. Sieving; Rs1 Knockout Mice Show Altered Transducin Translocation But Not Arrestin In Response To Light At Early Age. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2667.
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Pathology in X-linked retinoschisis disease is observed primarily in post-photoreceptor retinal structure and function. However, the robust expression of Rs1 protein in photoreceptor inner segments and the disruption and disorganization of photoreceptor pre-synaptic processes as early as P21 in Rs1-KO mice suggested that loss of Rs1 protein affects photoreceptor function at an early age. We investigated light-activated translocation of phototransduction proteins, transducin (Tα) and β-arrestin (β-Ar), as a marker for rod outer (ROS) and inner (IS) segment retinal function in young Rs1-KO mouse.
Dark-adapted WT and Rs1-KO anesthetized mice were exposed to light (6-60 sc-cd/m2) for 1h, after which eyes were enucleated and fixed. 100 µm retinal sections were analyzed for Tα and β-Ar immunoreactivity by confocal microscopy.
In WT mice Tα threshold for translocation from ROS to IS was 18 sc-cd/m2 at P21 and 12 sc-cd/m2 at P60. Rs1-KO mice exhibited Tα translocation by 60 sc-cd/m2 at P60 but the amount was greatly reduced and patchy. Rs1-KO mice at P21 showed presence of Tα but no translocation was observed even at 60 sc-cd/m2. b-Ar translocates from IS to ROS in response to light in both P21 and P60 WT and Rs1-KO mice at all light intensities tested.
The higher threshold for Tα translocation in Rs1-KO retina versus WT indicates either an early age reduction in light sensitivity or reduced capacity for light-activated mobilization of transducin. However, β-Ar translocation occurred at the lowest intensity (6 sc-cd/m2) in both Rs1-KO and WT. This also indicates that the ROS-IS translocation path appears to be intact and that the lack of Rs1 expression per se does not limit protein movement. The structural abnormalities in the Rs1-KO photoreceptors membranes (presumed from previous AFM studies of Rs1 interactions with artificial lipid membranes) may affect dissociation of Tα-subunit thus limiting translocation.
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