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David Krizaj, Lutz Birnbaumer, Peter Barabas; Canonical Trp Channels (Trpc1 and Trpc3) Regulate Neurotransmission And Visual Acuity In The Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4121.
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To analyze light-evoked responses and visual behavior in mice lacking vertebrate homologs of the Drosophila TRP channel. TRP channels play a fundamental role in invertebrate photoreceptor signaling. Their canonical (TRPC) homologs have been implicated in ip-RGC phototransduction, however, expression and function of specific TRPC isoforms in vertebrate retinas is unknown.
RT-PCR was used to analyze the expression of Trpc1 -7 genes in wild type, KO and Pde6brd1 mice. Mouse lines lacking Trpc1 (TRPC1-/-), Trpc3 (TRPC3-/-) and Trpc1/Trpc3 (TRPC1/3-/-) genes were tested for visual acuity and for light-evoked responses under photopic and scotopic conditions. Contrast sensitivity functions were obtained for optokinetic reflex (OKR) responses to moving sine-wave gratings using a virtual optomotor apparatus (Optomotry) at optimal drift velocities for photopic and scotopic vision, respectively. Electroretinographic (ERG) analysis was performed in anesthetized mice under scotopic and photopic conditions.
Trpc1 mRNA accounted for 78 ± 15% of the total canonical transcriptome in the mouse retina. Loss of rods in P90 Pde6brd1 retinas was associated with 77 ± 7% reduction in Trpc1 mRNA content. The amplitude of scotopic OKR responses in Sv129 wild type controls was 0.252 ± 0.003 cycles/degree. Scotopic acuity was increased in TRPC1-/- (0.272 ± 0.009 c/deg) and TRPC3-/- (0.292 ± 0.007 c/deg) animals. Given 88 ± 10% compensatory upregulation of Trpc3 mRNA in TRPC1-/- retinas we generated TRPC1/3-/- animals; their OKR was 0.308 ± 0.003 c/deg, significantly increased compared to controls (P<0.001). The scotopic a-wave was increased in TRPC1-/- eyes at high flash intensities and in TRPC1/3-/- eyes at all flash intensities (P<0.01). Increased b-wave amplitudes (20 ± 3%) were measured in double KO eyes. Photopic OKR responses in TRPC1-/- and TRPC3-/- animals were statistically indistinguishable from controls (0.412 ± 0.006 c/deg); however, a significant increase in photopic acuity was observed in TRPC1/3-/- animals (0.442 ± 0.005 cycles/deg).
These results show that TRPC1 channels, possibly in heteromeric association with TRPC3, negatively regulate rod signaling and scotopic visual behavior in mice. Influx of calcium through TRPC1/3 channels appears to modulate the photosensitivity, neurotransmission and/or the dynamic range of light-evoked signals in wild type rods.
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