Rhodopsin
Rhodopsin
Definition
Rhodopsin is the visual pigment that "senses" light in the rod cells of the retina.
Where is rhodopsin?
Rhodopsin is found at the back of the eye, in the retina. The retina is the area of the eye that senses light, interprets that information, and transmits it to the brain for further interpretation. Two types of light-sensing cells are found in the retina: rods and cones. In a simplified explanation, rod cells are responsible for black and white vision, whereas cone cells are responsible for color vision. This is true as far as it goes, but there are many more differences between rods and cones.
In rod cells, rhodopsin is responsible for phototransduction, the process of turning light into chemical and electrical energy. Rhodopsin is responsible for phototransduction in rod cells, but not in cone cells. Three different proteins, similar to rhodopsin, govern phototransduction in the cone cells. Each of these three phototransducers responds to a different color of light, which allows persons with normal color vision to see the entire color spectrum.
In order to understand more of the structure, function, and location of rhodopsin, a discussion of cells and cell membranes is necessary. Every human cell has a cell membrane that separates the environment inside the cell (intracellular environment) from the extracellular (out-side the cell) environment. Cell membranes are made up of lipids, which are hydrophobic substances. Hydrophobic literally means fear of water. Oil is an example of a hydrophobic substance. If oil is added to water, the oil will separate itself from the water. Basically, the lipids in the cell membrane form a similar water-excluding ball, but the inside of the ball will contain water (and other intracellular fluids). Each rhodopsin molecule crosses the cell membrane seven times, and each area of the protein in the cell membrane is called a transmembrane domain. These transmembrane domains (which are hydrophobic) dictate an interesting structure for rhodopsin. Imagine folding a hose seven times to hold it in your hand. The structure for rhodopsin is at least that complex. One reason to mention that rhodopsin has seven transmembrane domains is because that structure is common to G proteins, and rhodopsin is a G protein. G proteins are generally involved in a biological cascade. A biological cascade is a system where a small initial input (like a brief flash of light) can result in a rather large output.
How does rhodopsin turn light into a chemical signal?
Rhodopsin is a combination of two different molecules, retinal and opsin. Retinal is a derivative of vitamin A and opsin is a protein. When rhodopsin is not activated, retinal is in the 11-cis configuration. When light hits 11-cis retinal, it changes its shape to become alltrans retinal. This is the only light-sensitive step in vision (in the rod cells). What the configurations are called, and what those names mean is not as important as the fact that this light-dependent change in conformation results in light being converted into chemical energy.
Once retinal reaches the all-trans conformation, opsin also changes its shape. The new opsin-retinal complex is called metarhodopsin II. Metarhodopsin II is a semistable complex that is the active form of rhodopsin. Metarhodopsin II, unlike the inactive rhodopsin, is able to bind a protein called transducin. Each metarhodopsin II can bind to many transducins (literally hundreds). These transducins then cause a decrease in cGMP concentration, and one transducin molecule can cause the breakdown of more than 1,000 cGMP per second. One can clearly see why the G protein cascades are excellent systems for amplifying a signal.
Mutations in rhodopsin
Mutations in rhodopsin can result in two different disorders—retinitis pigmentosa and congenital stationary night blindness, Retinitis pigmentosa (RP) affects about one in 3,000 persons living in the United States, and about 1.5 million persons worldwide. Many mutations, not just mutations of the rhodopsin gene , lead to RP. The disorder may be inherited in an X-linked recessive fashion in 8% of all cases, an autosomal dominant fashion in 19% of cases, or as an autosomal recessive disorder in 19% of all cases. In the rest of the cases (54%), the mutations do not follow classical genetic patterns of inheritance . Mutations in rhodopsin have been found to cause approximately 20% of the autosomal dominant form of RP. The rhodopsin gene is located at the 3q locus of the chromosome .
Patients with retinitis pigmentosa exhibit symptoms that include night blindness, abnormal pigment accumulation in the retina, and a progressive decrease in the visual fields. The patient's vision decreases from the outermost edges in. The age of onset of the disorder may be as young as six months, but most patients experience the first symptoms between ages 10 and 30. In RP, the patient's rod cells usually degenerate first, followed by a loss of cone cells.
Symptoms may often present after a motor vehicle accident. Not only is the age of onset variable, but the severity of the disease is as well. Patients with the same mutation, even within the same family, exhibit differing severities of the disorder. Mutations in rhodopsin may also cause autosomal recessive cases of RP.
Congenital stationary night blindness (CSNB) is another disorder that can be caused by mutations in the rhodopsin gene. Patients with CSNB, as may be deduced from the name, experience night blindness. However, unlike RP, patients with CSNB do not experience degeneration (death) of cells of the retina (rod and cone cells). Patients with CSNB are thought to have an overactive transducin molecule, which prevents their rods from functioning normally. A mutation in transducin which also causes CSNB supports this theory, since this transducin is also thought to be overly active.
Treatment and management
No effective treatment for RP exists. However, new treatments are being explored for RP. Experiments in rats have shown that rod cells can be affected by gene therapy . Although gene therapy has not been successfully demonstrated as of this printing, at least the hope now exists that eventually gene therapy may be applied to the problem of RP. Previously, addition of a new gene into a non-dividing cell line had been thought to be technically insurmountable. Another experiment in rodents offers hope for those who have autosomal recessive RP. In rats with autosomal recessive RP, retinal pigment transplantation has successfully treated them according to Columbia University's Retinal Transplant newsletter. This technique might prove promising in humans.
Prognosis
The prognosis for persons with RP is extremely variable. Persons with CSNB will experience night blindness throughout their lives.
Resources
WEBSITES
"A guide to retinitis pigmentosa." The British Retinitis Pigmentosa Society. <http://www.brps.demon.co.uk/Graphics/G_Guide.html#SYMPTOMS>.
Robbins, Alexandra. "Congenital stationary night blindness." <http://130.132.19.190/thom/reviews/cnsb.html>.
Michael V. Zuck, PhD
Rhodopsin
Rhodopsin
Definition
Rhodopsin is the visual pigment that "senses" light in the rod cells of the retina.
Where is rhodopsin?
Rhodopsin is found at the back of the eye, in the retina. The retina is the area of the eye that senses light, interprets that information, and transmits it to the brain for further interpretation. Two types of light-sensing cells are found in the retina: rods and cones. In a simplified explanation, rod cells are responsible for black and white vision, whereas cone cells are responsible for color vision. This is true as far as it goes, but there are many more differences between rods and cones.
In rod cells, rhodopsin is responsible for phototransduction, the process of turning light into chemical and electrical energy. Rhodopsin is responsible for phototransduction in rod cells, but not in cone cells. Three different proteins, similar to rhodopsin, govern phototransduction in the cone cells. Each of these three phototransducers responds to a different color of light, which allows persons with normal color vision to see the entire color spectrum.
In order to understand more of the structure, function, and location of rhodopsin, a discussion of cells and cell membranes is necessary. Every human cell has a cell membrane that separates the environment inside the cell (intracellular environment) from the extracellular (outside the cell) environment. Cell membranes are made up of lipids, which are hydrophobic substances. Hydrophobic literally means "fear of water." Oil is an example of a hydrophobic substance. If oil is added to water, the oil will separate itself from the water. Basically, the lipids in the cell membrane form a similar water-excluding ball, but the inside of the ball will contain water (and other intracellular fluids). Each rhodopsin molecule crosses the cell membrane seven times, and each area of the protein in the cell membrane is called a transmembrane domain. These transmembrane domains (which are hydrophobic) dictate an interesting structure for rhodopsin. Imagine folding a hose seven times to hold it in your hand. The structure for rhodopsin is at least that complex. One reason to mention that rhodopsin has the seven transmembrane domains is because that structure is common to G proteins, and rhodopsin is a G protein. G proteins are generally involved in a biological cascade. A biological cascade is a system where a small initial input (like a brief flash of light) can result in a rather large output.
How does rhodopsin turn light into a chemical signal?
Rhodopsin is a combination of two different molecules, retinal and opsin. Retinal is a derivative of vitamin A, and opsin is a protein. When rhodopsin is not activated, retinal is in the 11-cis configuration. When light hits 11-cis retinal, it changes its shape to become all-trans retinal. This is the only light-sensitive step in vision (in the rod cells). What the configurations are called, and what those names mean is not as important as the fact that this light-dependent change in conformation results in light being converted into chemical energy.
Once retinal reaches the all-trans conformation, opsin also changes its shape. The new opsin-retinal complex is called metarhodopsin II. Metarhodopsin II is a semistable complex that is the active form of rhodopsin. Metarhodopsin II, unlike the inactive rhodopsin, is able to bind a protein called transducin. Each metarhodopsin II can bind to many transducins (literally hundreds). These transducins then cause a decrease in cGMP concentration, and one transducin molecule can cause the breakdown of more than 1,000 cGMP per second. One can clearly see why the G protein cascades are excellent systems for amplifying a signal.
Mutations in rhodopsin
Mutations in rhodopsin can result in two different disorders—retinitis pigmentosa and congenital stationary night blindness. Retinitis pigmentosa (RP) affects about one in 3,000 persons living in the United States, and about 1.5 million persons worldwide. Many mutations, not just mutations of the rhodopsin gene , lead to RP. The disorder may be inherited in an X-linked recessive fashion in 8% of all cases, an autosomal dominant fashion in 19% of cases, or as an autosomal recessive disorder in 19% of all cases. In the rest of the cases (54%), the mutations do not follow classical genetic patterns of inheritance . Mutations in rhodopsin have been found to cause approximately 20% of the autosomal dominant form of RP. The rhodopsin gene is located at the 3q locus of chromosome 3.
Patients with retinitis pigmentosa exhibit symptoms that include night blindness, abnormal pigment accumulation in the retina, and a progressive decrease in the visual fields. The patient's vision decreases from the outermost edges in. The age of onset of the disorder may be as young as six months, but most patients experience the first symptoms between ages 10 and 30. In RP, the patient's rod cells usually degenerate first, followed by a loss of cone cells.
Symptoms may often present after a motor vehicle accident. Not only is the age of onset variable, but the severity of the disease is as well. Patients with the same mutation, even within the same family, exhibit differing severities of the disorder. Mutations in rhodopsin may also cause autosomal recessive cases of RP.
Congenital stationary night blindness (CSNB) is another disorder that can be caused by mutations in the rhodopsin gene. Patients with CSNB, as may be deduced from the name, experience night blindness. However, unlike RP, patients with CSNB do not experience degeneration (death) of cells of the retina (rod and cone cells). Patients with CSNB are thought to have an overactive transducin molecule, which prevents their rods from functioning normally. A mutation in transducin, which also causes CSNB, supports this theory, since this transducin is also thought to be overly active.
Treatment
As of 2001, no effective treamtment for RP exists. However, new treatments are being explored for RP. Experiments in rats have shown that rod cells can be affected by gene therapy . Although gene therapy has not been successfully demonstrated as of this printing, at least the hope now exists that eventually gene therapy may be applied to the problem of RP. Previously, addition of a new gene into a non-dividing cell line had been thought to be technically insurmountable. Another experiment in rodents offers hope for those who have autosomal recessive RP. In rats with autosomal recessive RP, retinal pigment transplantation has successfully treated them according to Columbia University's Retinal Transplant newsletter. This technique might prove promising in humans.
Prognosis
The prognosis for persons with RP is extremely variable. Persons with CSNB will experience night blindness throughout their lives.
Resources
WEBSITES
"A guide to retinitis pigmentosa." The British Retinitis Pigmentosa Society. <http://www.brps.demon.co.uk/Graphics/G_Guide.html#SYMPTOMS>.
Robbins, Alexandra. "Congenital stationary night blindness." <http://130.132.19.190/thom/reviews/cnsb.html>.
Michael V. Zuck, PhD
rhodopsin
rhodopsin
rhodopsin
rho·dop·sin / rōˈdäpsən/ • n. a purplish-red light-sensitive pigment present in the retinas of humans and many other animal groups.