Disc shedding is the process by which

photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiation ...

s in the retina are renewed. The disc formations in the outer segment of photoreceptors, which contain the photosensitive

opsin Animal opsins are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become retinylidene proteins, but are usually still called opsins regardless. Most pro ...

s, are completely renewed every ten days.

Photoreceptors

The

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

contains two types of photoreceptor –

rod cells Rod cells are photoreceptor cells in the retina of the eye that can function in lower light better than the other type of visual photoreceptor, cone cells. Rods are usually found concentrated at the outer edges of the retina and are used in pe ...

and

cone cells Cone cells or cones are photoreceptor cells in the retina of the vertebrate eye. Cones are active in daylight conditions and enable photopic vision, as opposed to rod cells, which are active in dim light and enable scotopic vision. Most vertebr ...

. There are about 6-7 million cones that mediate

photopic vision Photopic vision is the vision of the eye under well-lit conditions (luminance levels from 10 to 108 cd/m2). In humans and many other animals, photopic vision allows color perception, mediated by cone cells, and a significantly higher vis ...

, and they are concentrated in the

macula The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal avas ...

at the center of the retina. There are about 120 million rods that are more sensitive than the cones and therefore mediate

scotopic vision In the study of visual perception, scotopic vision (or scotopia) is the vision of the eye under low-light conditions. The term comes from the Greek ''skotos'', meaning 'darkness', and ''-opia'', meaning 'a condition of sight'. In the human eye, c ...

. A vertebrate's photoreceptors are divided into three parts: * an outer segment that contains the photosensitive

s * an inner segment that contains the cell's metabolic machinery (

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

Golgi complex The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

ribosomes Ribosomes () are macromolecular machines, found within all cells, that perform biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to fo ...

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

) * a synaptic terminal at which contacts with second-order neurons of the retina are made

Discs

The photosensitive outer segment consists of a series of discrete membranous discs .Besharse, J.C., & Pfenninger, K.H. (1980). "Membrane assembly in retinal photoreceptors: I. Freeze-fracture analysis of cytoplasmic vesicles in relationship to disc assembly", The Journal of Cell Biology, 87, 451-463. While in the rod, these discs lack any direct connection to the surface membrane (with the exception of a few recently formed basal discs that remain in continuity with the surface), the cone's photosensitive membrane is continuous with the surface membrane. The outer segment (OS) discs are densely packed with

rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...

for high-sensitivity light detection.Chuang, J., Zhao, Y., & Sung, C. (2007). "SARA-regulated vesicular targeting underlies formation of the light sensing organelle in mammalian rods", Cell, 130, 535-547. These discs are completely replaced once every ten days and this continuous renewal continues throughout the lifetime of the sighted animal. After the

s are synthesized, they fuse to the plasma membrane, which then invaginates with discs budding off internally, forming the tightly packed stacks of outer segment discs. From translation of opsin to formation of the discs takes just a couple of hours.

Shedding

Disc shedding was first described by RW Young in 1967. Discs mature along with their distal migration; aged discs shed at the distal tip and are engulfed by the neighboring

retinal pigment epithelial The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ...

(RPE) cells for degradation. One early study showed that cones may not experience the cone shedding as rods do and may renew by replacing molecular constituents individually. However, other studies do show that at least ''some'' mammalian cones do shed their discs as a normal ongoing process. Each day about one tenth of the length of the outer segment is lost, so that after ten days the entire outer segment has been replaced. Regulating factors are involved at each step. While disc assembly is mostly genetically controlled, disc shedding and the subsequent RPE phagocytosis appear to be regulated by environmental factors like light and temperature.Nguyen-Legros, J., & Hicks, D. (2000). "Renewal of photoreceptor outer segments and their phagocytosis by the retinal pigment epithelium", International Review of Cytology, 196, 245-313. The timing of shedding follows a

circadian rhythm A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the env ...

according to

neuromodulators Neuromodulation is the physiology, physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic receptor, metabotropic, G protein-coupled rece ...

, namely dopamine and melatonin. Melatonin is synthesized by the photoreceptors at night, and is inhibited by light and dopamine, so triggers cone disc shedding. Dopamine production is stimulated by light and inhibited by dark and melatonin, so triggers cone disc shedding. Importantly, rod discs are shed during the day and cone discs are shed during the night.LaVail, M.M. (1980). "Circadian nature of rod outer segment disc shedding in the rat", Investigative Ophthalmology & Vision Science, 19(4), 407-411.

Mechanism

Traditional theories

One grey area in the entire mechanism of outer segment disc shedding is in what exactly triggers the detachment of the discs and how they are transported out of the OS and phagocytosed by the RPE cells. Some studies suggest that disc detachment precedes engulfment by the RPE cells, and that an active process in the rod outer segment severs the disc.Anderson, D.H., Fisher, S.K., & Steinberg, R.H. (1978). "Mammalian cones: disc shedding, phagocytosis, and renewal", Investigative Ophthalmology & Visual Science, 17(2), 117-33. However, other studies observed RPE cell processes intruding into the OS during disc detachment. These processes are structurally similar to processes formed by macrophages during

phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

and were accordingly referred to as

pseudopodia A pseudopod or pseudopodium (: pseudopods or pseudopodia) is a temporary arm-like projection of a eukaryotic cell membrane that is emerged in the direction of movement. Filled with cytoplasm, pseudopodia primarily consist of actin filaments and ...

. The study suggested that these pseudopodia were the organelles of phagocytosis and that they may play a direct role in disc detachment.{{cite journal , last1=Besharse , first1=Joseph C. , last2=Spratt , first2=Gwendolyn , last3=Forestner , first3=Donna M. , title=Light-evoked and kainic-acid-induced disc shedding by rod photoreceptors: Differential sensitivity to extracellular calcium , journal=The Journal of Comparative Neurology , date=8 September 1986 , volume=251 , issue=2 , pages=185–197 , doi=10.1002/cne.902510205

Recent research

A 2007 paper offers a third theory that builds on recent evidence that suggests that rhodopsin-deficient mice fail to develop OSS.Humphries, M.M., Rancourt, D., Farrar, G.J., Kenna, P., Hazel, M., Bush, R.A., et al. (1997). "

Retinopathy Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically in ...

induced in mice by targeted disruption of the rhodopsin gene", Nat. Genet., 15, 216-219.Lem, J., Krasnoperova, N.V., Calvert, P.D., Kosaras, B., Cameron, D.A., Nicolo, M., et al. (1999). "Morphological, physiological, and biochemical changes in rhodopsin knockout mice", Proc. Natl. Acad. Sci. USA, 96, 736-741. Researchers at Cornell hypothesized that rhodopsin itself has a role in OS biogenesis, in addition to its role as a phototransduction receptor. While the molecular basis underlying rhodopsin's participation in OS development is unknown, emerging evidence suggests that rhodopsin's cytoplasmic C-terminal tail bears an “address signal” for its transport from its site of synthesis in the rod cell body to the OS.Tai, A.W., Chuang, J.-Z., Bode, C., Wolfrum, U., & Sung, C.-H. (1999). "Rhodopsin’s carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1", Cell, 95, 779-791.Deretic, D., Williams, A.H., Ransom, N., Morel, V., Hargrave, P.A, & Arendt, A. (2005). "Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4)", Proc. Natl. Acad. Sci. USA, 102, 3301-3306.

References

Eye Histology Photoreceptor cells