and Jürgen Roth2
Medical University of Vienna, Vienna, Austria
University of Zurich, Zurich, Switzerland
Photoreceptor Cells of the Retina: Signaling of Light
Photoreceptor cells are part of the inner sensory retina and become activated by light. Two major types of photoreceptor cells exist, and they reside in specific regions in the retina. The rod cells, which contain the photopigment rhodopsin and occupy the periphery of the retina, are exceptionally sensitive to low light levels and specialized for night vision. The cone cells occupy central parts of the retina and are specialized for high resolution at high light levels and for color detection. Three types of cone cells exist, which permits discrimination of blue, green and red depending on the photopigment they contain.
Both rod and cone cells are elongated, highly polarized cells. Their main structural and functional features are the inner and outer segments above the nuclear region. Infranuclear lies the synaptic region, establishing contact with interneurons, which transmit light-induced electrical signals to the retinal ganglion cells. Inner segments contain numerous elongated mitochondria in addition to endoplasmic reticulum and the Golgi apparatus. The border between the inner and outer segment in rod cells is indicated by open arrows in panel a and shown at higher magnification in panels b (cross section) and C (longitudinal section). This demonstrates that inner and outer segments are connected by a modified cilium (asterisk in panel c) with a 9 + 0 symmetry. The light-sensing outer segments are derived from the modified cilium.
In mammals, the outer segments of rods and cones are cylindrically shaped. Outer segments contain stacks of double membrane disks (details shown in Fig. 133), in which the photosensitive visual pigment molecules are embedded. The various components of the discs are synthesized in the inner segments and transported into the outer segments through the narrow cytoplasm surrounding the connecting cilium (panel b). The visual pigment present in the disc membranes of rods and cones is rhodopsin, a multispanning membrane protein that detects photons. It bears two N-linked oligosaccharides that are required for its full signal transduction activity. Rhodopsin consists of opsin apoprotein to which the chromophore is covalently linked. The chromophore is vitamin A1-derived 11 cis-retinal. Its extended structure accounts for its visible light absorption properties. Upon photon capture, the 11 cis-retinal is photoisomerized into all-trans-retinal. This initiates a signaling cascade that results finally in hyperpolarized cells.
The apical ends of the outer segments of cones and rods are embedded in the retinal pigment epithelium that contains melanin granules, which absorb excess light and prevent its reflection. Between the two cell types lies the interphotoreceptor matrix, which functions as a glue. Separation of the two layers results in retinal detachment, with severe consequences for vision. The function of the retinal pigment epithelium with regard to outer segment turnover is discussed in Fig. 133. In addition to its nutritional function for the retina, the retinal pigment epithelium has an essential role for rhodopsin regeneration in the visual cycle. Photoisomerized rhodopsin disassembles in opsin and all-trans-retinal. The all-trans-retinal is transported to the pigment epithelium, enzymatically oxidized and re-isomerized to 11 cis-retinal.
Borhan B, Souto M, Imai H, Shichida Y, Nakanishi K (2000) Movement of retinal along the visual transduction pathway. Science 288:2209
Chuang JZ, Zhao Y, Sung CH (2007) SARA-regulated vesicular targeting underlies formation of the light-sensing organelle in mammalian rods. Cell 130:535
Gilliam JC, Chang JT, Sandoval IM, Zhang Y, Li T, Pittler ST, Chiu W, Wensel TG (2012) Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration. Cell 151:1029
Kaushal S, Ridge K, Khorana H (1994) Structure and function in rhodopsin: the role of asparagine-linked glycosylation. Proc Natl Acad Sci USA 91:4024
Masland R (2001) The fundamental plan of the retina. Nat Neurosci 4:877
Menon S, Han M, Sakmar T (2001) Rhodopsin: structural basis of molecular physiology. Physiol Rev 81:1659
Obata S, Usukura J (1992) Morphogenesis of the photoreceptor outer segment during postnatal development in the mouse (BALB/c) retina. Cell Tissue Res 269:39
Sung C-H, Chuang J-Z (2010) The cell biology of vision. J Cell Biol 190:953
Wang S et al. (2014) The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration. PLos Biol 12:e1001847
Magnification: ×8,200 (a); ×180,000 (b); ×65,000 (c)
Photoreceptor Cells of the Retina: Light-Induced Apoptosis
Photoreceptor cells are highly polarized and specialized cells unable to undergo mitotic division. However, they display a remarkable phenomenon in that the light-sensitive rod and cone outer segments are continuously renewed while the remainder of the cells are relatively stable. In panel a, the detailed fine structural organization of rod outer segments is shown. It consists of parallel arranged, densely packed membrane discs that in rods are separated from the plasma membrane (inset in panel a). The space between the apical parts of the outer segments is filled with processes of the pigment epithelium.
Although still a matter of debate, the formation of the outer segment membrane discs is proposed to occur through fusion of rhodopsin-containing membrane vesicles that represent the disc precursors. Newly formed discs then move from the base of the outer segment to their tip. Tips containing discs finally shed and are phagocytized and degraded by the pigment epithelium. Thus, discs are continuously eliminated and renewed. The retinal pigment epithelia, which represents professional phagocytes, degrade photoreceptor discs and are involved in the recycling of their components. The renewal of the rod outer segments seems to be regulated and to follow a circadian rhythm. Related to their differential visual function, phagocytosis of rod discs commences shortly after the onset of light, whereas phagocytosis of cone discs occurs at the onset of darkness.
The phagocytic activity of the retinal pigment epithelia is also of importance when rapidly changing illumination conditions require adaptation and following photoreceptor damage resulting in apoptosis. Not only in relation to the circadian rhythm but also in abruptly increasing light intensity, the light sensitivity of rods requires downregulation. This occurs, at least in part, through changes in the pattern of disc shedding from the outer segment tips and their phagocytosis by the retinal pigment epithelium. In addition, the rhodopsin levels are adapted to low and high light levels.
Panel b depicts the enormous structural alterations occurring in rod outer segments after acute bright light exposure (up to 1,000 lx for 2 h) of albino rat eye. At higher light intensities, apoptotic photoreceptor death occurs. White light and certain wavelengths of the visible spectrum, namely blue light, preferentially induce photoreceptor apoptosis in vertebrates. In mice, the availability of rhodopsin during light exposure is one determinant for the sensitivity to light-induced apoptosis. With some delay to photoreceptor cells, apoptosis of retinal pigment epithelium takes place. Collectively, these data indicate that retinal degeneration can result from prolonged exposure to intense light. In experimental settings with mice, evidence for two different apoptotic pathways in light-induced retinal degeneration was obtained. The pathway triggered by bright light is independent of transducin-mediated signaling but requires activation of rhodopsin. The other one induced by low-intensity light depends on transducin-mediated signaling.