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Intra-retinal visual cycle required for rapid and complete cone dark adaptation


Daytime vision is mediated by retinal cones, which, unlike rods, remain functional even in bright light and dark-adapt rapidly. These cone properties are enabled by rapid regeneration of their pigment. This in turn requires rapid chromophore recycling that may not be achieved by the canonical retinal pigment epithelium visual cycle. Recent biochemical studies have suggested the presence of a second, cone-specific visual cycle, although its physiological function remains to be established. We found that the Müller cells in the salamander neural retina promote cone-specific pigment regeneration and dark adaptation that are independent of the pigment epithelium. Without this pathway, dark adaptation of cones was slow and incomplete. Notably, the rates of cone pigment regeneration by the retina and pigment epithelium visual cycles were essentially identical, suggesting a possible common rate-limiting step. Finally, we also observed cone dark adaptation in the isolated mouse retina.

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Figure 1: Effect of bleach on pigment content in salamander photoreceptors in dissociated and intact retina.
Figure 2: Effect of bleach on sensitivity in salamander photoreceptors in dissociated and intact retina.
Figure 3: Effect of the Müller cell inhibitor L-α-AAA on the recovery of cone sensitivity following a bleach.
Figure 4: Rod and cone responses from salamander whole-retina ERG recordings.
Figure 5: Kinetics of cone dark adaptation from whole-retina ERG recordings.
Figure 6: Rod and cone responses from mouse whole-retina ERG recordings.


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We thank R. Crouch for the generous gift of 11-cis retinal and 11-cis retinol, P. Ala-Laurila for his expert assistance with the analysis of microspectrophotometric data and K.-W. Yau, P. Lukasiewicz, J. Corbo, R. Crouch and P. Ala-Laurila for comments on the manuscript. This work was supported by a Career Development Award from Research to Prevent Blindness, the Karl Kirchgessner Foundation and NIH grants EY 019312 (V.J.K.), EY 01157 (M.C.C.) and EY 02687 (Department of Ophthalmology and Visual Sciences at Washington University).

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Correspondence to Vladimir J Kefalov.

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Wang, JS., Estevez, M., Cornwall, M. et al. Intra-retinal visual cycle required for rapid and complete cone dark adaptation. Nat Neurosci 12, 295–302 (2009).

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