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J.-S. Wang, V. J. Kefalov; Functional Cone-Specific Visual Cycle in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6146.
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The existence of a cone-specific visual cycle in the retina has been suggested by biochemical studies from cone-dominant species such as chicken and ground squirrel. However, its presence in rod-dominant mammals, including mouse, is controversial. We investigated what, if any, role a retina visual cycle plays in the function of mouse cones during dark and background adaptation.
Using suction electrode, we recorded membrane currents from single mouse rods and cones. Using trans-retinal ERG and with synaptic transmission inhibited pharmacologically, we recorded photoreceptor-generated a-waves. Intact retinas, removed from eyecup and pigment epithelium, were bleached by 500 nm light for 40 seconds, and then dark adapted prior to recording. We used wild type (WT) mice for rod recordings and Transducin (Tr-/-), Rhodopsin (Rh-/-) and Nrl (Nrl-/-) knockout mice for cone recordings.
In both single cell and ERG recordings, bleaching WT retina reduced rod sensitivity over 100-fold. In contrast, cone sensitivity in Tr-/- retina recovered in less than 5 minutes to 1/3 of its dark-adapted level with full amplitude recovery. Thus, mouse retina promoted cone, but not rod, pigment regeneration independently of the pigment epithelium. Cone recovery was blocked by the Müller cell specific inhibitor L--Amino Adipic Acid (L--AAA) but could be restored by exogenous 11-cis-retinol. Pre-incubation of the retina in L--AAA also reduced 9.5-fold the background light required to reduce sensitivity 50% of dark adapted level, from 11,400 R* s-1 to 1,200 R* s-1. Thus, the retina visual cycle extended the dynamic range of cones in background light. The rate and extent of recovery of Rh-/- cones were comparable to these of Tr-/- cones. In contrast, bleached cones in Nrl-/- retina took 4 hours to recover.
Our physiological studies establish the function of a cone-specific visual cycle in mouse retina independent of the pigment epithelium and involving 11-cis-retinol and the Müller cells. This pathway promotes rapid dark adaptation in cones and extends their dynamic range in bright background light. The lack of effect of rhodopsin deletion on cone recovery indicates that the recycling of chromophore by the retina is independent of the rod visual cycle. The slow recovery of Nrl-/- cones most likely reflects the significantly increased ratio of cone cells to Müller cells in the Nrl-/- retina.
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