Review series The cell biology of vision

Correspondence to Ching-Hwa Sung: chsung@med.cornell. edu Abbreviations used in this paper: CC, connecting cilium; IFT, intraflagellar transport; IS, inner segment; OS, outer segment; PI3P, phosphatidylinositol 3-phosphate; RPE, retinal pigment epithelium; SARA, Smad anchor for receptor activation. Looking at the big picture: the retina is a neural circuit composed of different cell types The eye is an optical device that transmits and focuses light onto the neural retina (Fig. 1 A). The retina, a 0.2-mm-thick central nervous tissue, is the first station of the visual system. In addition to acting as a light receiver, the retina carries out considerable image processing through circuits that involve five main classes of cells (i.e., photoreceptors, bipolar cells, amacrine cells, horizontal cells, and ganglion cells; Fig. 1 B). These processes collectively amplify, extract, and compress signals to preserve relevant information before it gets transmitted to the midbrain and the thalamus through the optical nerves (axons of the ganglion cells; for review see Baccus, 2007). The retinal information received by the midbrain is processed to control eye movement, pupil size, and circadian photoentrainment (Huberman et al., 2008). Only the retinal input that terminates at the lateral geniculate nucleus of the thalamus is processed for visual perception and gets sent to the visual cortex. There, information about shade, color, relative motion, and depth are all combined to result in one’s visual experience. The vertebrate retina has an orderly laminated structure. The nuclei and processes of the retinal cells are segregated into alternate, anatomically distinctive layers (see legends in Fig. 1 C). Photoreceptors lie in the outer part of the retina, the region farthest from incoming light. Light passes through transparent inner retinal layers before it can be captured by the photoreceptor. Though such an organization may seem counterintuitive, it allows the retinal pigment epithelial (RPE) cells that lie juxtaposed to the apical side of the photoreceptors to absorb scattered light or light unabsorbed by the photoreceptors. Visual perception begins when the captured photon isomerizes the chromophore conjugated with the visual pigment in the photoreceptor cell. The photoexcited visual pigment then initiates a signal transduction cascade that amplifies the signal and leads to the closure of cation channels on the plasma membranes. As a result, the cells become hyperpolarized. The change in membrane potential is sensed by the synapses, which react by releasing fewer neurotransmitters (see more in Box 1; for review see Yau and Hardie, 2009). This information is relayed to the bipolar cells, and subsequently, the ganglion cells via a forward pathway. This information is also modified by their lateral interactions with the interneurons-amacrine cells and horizontal cells. Humans and other higher primates (but not other mammals) have foveas that are 700-μm-diameter foci near the central retina. The fovea has the highest visual acuity in comparison with other parts of the retina due to several structural and compositional modifications of this region. For example, the cell bodies of the proximal retinal neurons have been shifted to the side, enabling light paths to enter photoreceptors with minimal distortion (Fig. 1 A, boxed area). In addition, the fovea primarily consists of cone photoreceptors. The cone system has a higher resolution; each fovea cone is connected to only one bipolar and one ganglion cell. In other areas of the retina, each bipolar cell and ganglion cell serves multiple photoreceptors. Cones and rods are the two types of photoreceptors. Cones mediate vision in bright light, including color vision. Cones are named after their conically shaped light-sensing outer segments (OS). The OS is a modified cilium, a light-sensing organelle in which phototransduction occurs. The cone OS is commonly considered as a structure containing an orderly stack of membranous laminella that are continuous to the plasma membrane and form a highly convoluted surface membrane. Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude. Phototransduction—the process in which absorbed photons are converted into electrical responses—is the first stage of visual processing, and occurs in the outer segment, the light-sensing organelle of the photoreceptor cell. Studies of genes linked to human inherited blindness have been crucial to understanding the biogenesis of the outer segment and membrane-trafficking of photoreceptors. Review series