The Cone-specific visual cycle

Cone photoreceptors mediate our daytime vision and function under bright and rapidly-changing light conditions. As their visual pigment is destroyed in the process of photoactivation, the continuous function of cones imposes the need for rapid recycling of their chromophore and regeneration of their pigment. The canonical retinoid visual cycle through the retinal pigment epithelium cells recycles chromophore and supplies it to both rods and cones. However, shortcomings of this pathway, including its slow rate and competition with rods for chromophore, have led to the suggestion that cones might use a separate mechanism for recycling of chromophore. In the past four decades biochemical studies have identified enzymatic activities consistent with recycling chromophore in the retinas of cone-dominant animals, such as chicken and ground squirrel. These studies have led to the hypothesis of a cone-specific retina visual cycle. The physiological relevance of these studies was controversial for a long time and evidence for the function of this visual cycle emerged only in very recent studies and will be the focus of this review. The retina visual cycle supplies chromophore and promotes pigment regeneration only in cones but not in rods. This pathway is independent of the pigment epithelium and instead involves the Müller cells in the retina, where chromophore is recycled and supplied selectively to cones. The rapid supply of chromophore through the retina visual cycle is critical for extending the dynamic range of cones to bright light and for their rapid dark adaptation following exposure to light. The importance of the retina visual cycle is emphasized also by its preservation through evolution as its function has now been demonstrated in species ranging from salamander to zebrafish, mouse, primate, and human.