Disc shedding

Disc shedding is the process by which photoreceptors in the eye are renewed. The retina contains two types of photoreceptor – rod cells and cone cells. There are about 6-7 million cones that provide color vision to the eye, and they are very concentrated in a central spot in the retina, called the macula. However, the rods are much more numerous – about 120 million – and are also more sensitive than the cones. These rods are responsible for scotopic (night) vision, our most sensitive motion detection, and our peripheral vision. Disc shedding is the process by which photoreceptors in the eye are renewed. The retina contains two types of photoreceptor – rod cells and cone cells. There are about 6-7 million cones that provide color vision to the eye, and they are very concentrated in a central spot in the retina, called the macula. However, the rods are much more numerous – about 120 million – and are also more sensitive than the cones. These rods are responsible for scotopic (night) vision, our most sensitive motion detection, and our peripheral vision. Vertebrate photoreceptors are composed of a photosensitive outer segment, an inner segment that contains the cell’s metabolic machinery (endoplasmic reticulum, Golgi complex, ribosomes, mitochondria), and a synaptic terminal at which contacts with second-order neurons of the retina are made. The photosensitive outer segment is connected to the inner segment by a modified, nonmotile cilium, and consists of a series of discrete membranous discs that are apparently derived from the plasma membrane in the region of the connecting cilium. 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 for high-sensitivity light detection. These discs are completely replaced once every ten days and this continuous renewal continues throughout the lifetime of the sighted animal. Opsin is synthesized on the rough endoplasmic reticulum and is an integral membrane protein. Its signal peptide is at the N-terminus but is not cleaved off. The protein is co-translationally glycosylated and the protein’s carbohydrates are modified in the Golgi, before transfer to the plasma membrane. The membrane invaginates and disks bud off internally, forming the tightly packed stacks of outer segment disks. From translation of opsin to formation of the disks takes just a couple of hours. In a famous 1967 paper – The Renewal of Photoreceptor Cell Outer Segments – Professor Richard Young described his observations that new discs are assembled at the base of the outer segment – the ciliary plasmalemma – by incorporating proteins and lipids that are synthesized and transported from the inner segment. Discs mature along with their distal migration; aged discs shed at the distal tip and are engulfed by the neighboring retinal pigment epithelial cells for degradation. While many other enzymes and metabolically active proteins do turn over eventually, the photoreceptors shed the ends of their outer segments daily. 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. In a pulse-chase experiment, Young and his co-workers showed the migration of newly synthesized opsin from the ciliary stalk to the end of the outer segment, which is ultimately phagocytosed by the RPE cell. 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. Circadian rhythms that use neuromodulators such as adenosine, dopamine, glutamate, serotonin, and melatonin, rhythmically control disc shedding. Endogenous dopamine and melatonin seem to be the light and dark signal, in particular. Their method of action is simply as follows: melatonin activates rod photoreceptor disc shedding. It is synthesized by the photoreceptors at night, and is inhibited by light and dopamine. Acting in an opposite manner, dopamine, which is synthesized by amacrine and interplexiform cells is stimulated by light and inhibited by dark and melatonin. It is important to understand that, because of these rhythms, rod outer segment discs are shed at the onset of light (in the morning) and cone outer segments are shed at the onset of darkness (at dusk), both circadian processes.