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P. Barabas, W. Huang, W. Xing, A. Rao, Y.-Z. Le, C.-K. J. Chen, D. Krizaj; Store-Operated Calcium Entry Sustains Increased Calcium Level in Photoreceptor Cells and Affects Vision in the Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4133.
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Photoreceptor cells contain a store-operated system, which consists of Ca-permeable channels in the plasma membrane and STIM1 (stromal interaction molecule 1), a store-depletion EF sensor within the endoplasmic reticulum. Depletion of calcium stores activates store-operated calcium entry (SOCE) across plasma membrane SOC channels through STIM1 activation. We characterized the functional role of SOCE in mammalian vision by selectively eliminating STIM1 from rod and cone photoreceptors.
We developed mouse lines in which STIM1 was conditionally knocked out (cKO) in either rods or cones. STIM1 and Cre recombinase expression was determined with RT-PCR, Western blot and immunofluorescence. Fura-2 calcium imaging was performed in dissociated cells from control and cKO mouse retinas. The visual function was tested using flash ERG and the optomotor tracking response.
IHC revealed photoreceptor-specific expression of Cre and deletion of the STIM1 signals from targeted photoreceptor populations. Significant changes in visual acuity were observed for both rod and cone STIM1 cKO mouse lines. Rod cKOs exhibited lower scotopic acuity (0.239 ± 0.013 c/deg) compared to wild type (0.256 ± 0.004 c/deg) and Cre+fl-/fl- control animals (0.254 ± 0.007 c/deg) with no difference in photopic acuity. Cone cKOs were characterized by a decreased photopic acuity (0.358 ± 0.007 c/deg vs 0.384 ± 0.007 c/deg in controls) and no change in scotopic acuity. Photopic vision deficits developed over 6-15 weeks after birth. Baseline [Ca2+]i in light-adapted rods was substantially decreased in cKO rods from 97 ± 6 nM in control wild type to 64 ± 11 nM in rod cKO animals whereas no such difference was observed in Müller cells. SOCE responses in isolated cKO photoreceptors were significantly decreased with respect to controls in both response amplitude and ratio of cells expressing this phenomenon.
Loss of STIM1 from rods selectively compromises rod vision whereas selective elimination of STIM1 from cones causes photopic vision deficits. The observed visual phenotypes suggest that STIM1-stimulated store-operated calcium entry in photoreceptors significantly contributes to the regulation of steady-state [Ca2+]i and the flow of visual information from photoreceptors to higher order visual centers.
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