Molecular bases of rod and cone differences

Following exposure of our eye to very intense illumination, we experience a greatly elevated visual threshold, that takes tens of minutes to return completely to normal. The slowness of this phenomenon of "dark adaptation" has been studied for many decades, yet is still not fully understood. Here we review the biochemical and physical processes involved in eliminating the products of light absorption from the photoreceptor outer segment, in recycling the released retinoid to its original isomeric form as 11-cis retinal, and in regenerating the visual pigment rhodopsin. Then we analyse the time-course of three aspects of human dark adaptation: the recovery of psychophysical threshold, the recovery of rod photoreceptor circulating current, and the regeneration of rhodopsin. We begin with normal human subjects, and then analyse the recovery in several retinal disorders, including Oguchi disease, vitamin A deficiency, fundus albipunctatus, Bothnia dystrophy and Stargardt disease. We review a large body of evidence showing that the time-course of human dark adaptation and pigment regeneration is determined by the local concentration of 11-cis retinal, and that after a large bleach the recovery is limited by the rate at which 11-cis retinal is delivered to opsin in the bleached rod outer segments. We present a mathematical model that successfully describes a wide range of results in human and other mammals. The theoretical analysis provides a simple means of estimating the relative concentration of free 11-cis retinal in the retina/RPE, in disorders exhibiting slowed dark adaptation, from analysis of psychophysical measurements of threshold recovery or from analysis of pigment regeneration kinetics.

Why do vertebrates use rods and cones that hyperpolarize, when in insect eyes a single depolarizing photoreceptor can function at all light levels? We answer this question at least in part with a comprehensive assessment of ATP consumption for mammalian rods from voltages and currents and recently published physiological and biochemical data. In darkness, rods consume 10(8) ATP s(-1), about the same as Drosophila photoreceptors. Ion fluxes associated with phototransduction and synaptic transmission dominate; as in CNS, the contribution of enzymes of the second-messenger cascade is surprisingly small. Suppression of rod responses in daylight closes light-gated channels and reduces total energy consumption by >75%, but in Drosophila light opens channels and increases consumption 5-fold. Rods therefore provide an energy-efficient mechanism not present in rhabdomeric photoreceptors. Rods are metabolically less "costly" than cones, because cones do not saturate in bright light and use more ATP s(-1) for transducin activation and rhodopsin phosphorylation. This helps to explain why the vertebrate retina is duplex, and why some diurnal animals like primates have a small number of cones, concentrated in a region of high acuity.

Phototransduction is the process by which a photon of light captured by a molecule of visual pigment generates an electrical response in a photoreceptor cell. Vertebrate rod phototransduction is one of the best-studied G protein signaling pathways. In this pathway the photoreceptor-specific G protein, transducin, mediates between the visual pigment, rhodopsin, and the effector enzyme, cGMP phosphodiesterase. This review focuses on two quantitative features of G protein signaling in phototransduction: signal amplification and response timing. We examine how the interplay between the mechanisms that contribute to amplification and those that govern termination of G protein activity determine the speed and the sensitivity of the cellular response to light.