Gene therapy for color blindness is an experimental gene therapy that aims to convert blind individuals congenally into trichromat by introducing their own photopigment genes. Although partial color blindness is considered to be only mild and controversial disability whether it is even a nuisance, it is a condition that affects many people, especially men. Full color blindness, or achromatopsia, is very rare but more severe. Although it has never been shown in humans, animal studies have shown that it is possible to provide color vision by injecting genes from lost fotopigation using gene therapy. In 2014 there is no medical agency offering this treatment, and no clinical trials are available for volunteers.
Video Gene therapy for color blindness
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The retina of the human eye contains photoreceptive cells called cones that allow for color vision. A normal trichromate individual has three different conical types to distinguish different colors in the visible spectrum from 380 nm to 740 nm. These three cone types are cone-shaped L, M, and S, and each type is sensitive to a specific light-length range depending on what the fotopigment contains. More specifically, L cone absorbs about 560 Âμm, the M cone absorbs close to 530 Âμm, and the cone S absorbs near 420 n nm. Contrary to popular belief, peak absorption frequencies for L, M, and S cones do not exactly match the wavelengths of red, green, and blue. In contrast, the peak frequency for L cone is orange, yellowish green in conical M, and blue-violet in S cone. This cone transduces absorbed light into electrical information to pass on to neurons in the retina such as retinal bipolar cells and retinal ganglion cells, before it reaches the brain.
Signals from different cones are added or subtracted from each other to process incoming light colors. For example, the red color stimulates L more than the cone, while the green color stimulates L and M more than S cone. The colors felt in the opposing process, such as red and green are considered contradictory, such as blue and yellow, black and white.
The loci gene encodes for fotopigments: M-opsin and L-opsin are located near the X chromosome and are highly polymorphic. Among the populations, some have genes removed for M photopigment on the X chromosome (as in deuteranopia), while others have gene mutation forms (such as in deuteranomaly). Individuals who can reveal only two types of opsins in a cone are called dichromats. Since men only have one copy of X chromosome, dichromatism is much more common among men. With only two types of cones, the dichromats are less able to distinguish between the two colors. In the most common form of color blindness, the deuteranope has difficulty distinguishing red and green. This is demonstrated by their poor performance in the Ishihara test. Although dichromatism poses little problems in everyday life, the dichromates may find some color-coded diagrams and maps that are hard to read.
Less common forms of dichotomy include protoanopia (lack of L-cones), and tritanopia (lack of S-cone). If one does not have two types of fotopigment, they are considered monochromate. People who do not have three types of fotopigment are said to have complete color blindness or achromatopsia. Color blindness can also occur due to damage to the visual cortex in the brain.
Maps Gene therapy for color blindness
Theory
Experiments using various mammals (including primates) indicate that it is possible to give color vision to animals by introducing an opsin gene that was not previously possessed by animals. Using adeno viral-related (rAAV) recombinations as vectors, cDNAs of the opsin gene found in L or M cones may be sent to some conical fractions within the retina via subretinal injection. After getting the gene, the cone begins to express a new fotopigment. The therapeutic effect lasts until the cones die or the DNA inserted is lost inside the cone.
While gene therapy for humans has been going on with some success, gene therapy for humans to get color vision has not been sought to date. However, demonstrations using multiple mammals (including primates such as squirrel monkeys) suggest that therapy should be appropriate for humans as well. Theoretically it is also possible for trichromats to be "upgraded" to tetrachromate by introducing a new opsin gene.
Motivation
The goal of gene therapy is to make some cones in the individual retina dichromate to express the missing fotopigment. Although partial color blindness is regarded as a mild defect and even a benefit in certain circumstances (such as blotching object spots), it can pose challenges for many jobs such as Law Enforcement, Airline pilots, railroad workers and military service. More generally, color codes in maps and images may be difficult to read for individuals with color blindness.
Since only one gene code for photopigment and genes is expressed only in the retina, it is relatively easy to treat with gene therapy compared to other genetic diseases. However, there is still the question of whether this therapy is beneficial, for an individual to undergo invasive subretinal injection to temporarily treat conditions that are more of an inconvenience than a nuisance.
However, complete color blindness, or achromatopsia, is very rare but more severe. Indeed, the acromate can not see any color, has a strong photophobia (blindness in full sun), and reduced visual acuity (generally 20/200 after correction).
In addition, the study may have strong implications for other cone genetic therapy. Other cone diseases such as Leber congenital amaurosis, stem rhythm dystrophy, and some types of maculopathies may be treated using the same technique as gene therapy used for color blindness.
Research so far
There has been ongoing research for gene therapy to treat Leber's innate amaurosis, a genetic disorder of photoreceptors that can cause vision loss and blindness. This treatment uses AAV vectors and is delivered in the same way as gene therapy for color blindness.
Jacobs et al. published their research in the journal: Science in 2007, at their work introducing the human L-cone fotopigment in mice. Because mice have only cone S and M cones, they are dichromates. The researchers replaced M-opsin with L-opsin cDNA on the X chromosome of some mice. By breeding these "knock-in" transgenic rats, they produce heterozygous females with both M cone and L cone. These mice have improved color vision and have obtained trichromation, as tested by electroretinogram and behavioral tests. However, it is more difficult to apply in the form of gene therapy.
In a paper published in the journal: Visual Neuroscience by Mauck et al., The researchers used a recombinant AAV vector to introduce the green fluorescence protein gene (GFP) in a gerbil cone. The genetic inserts are designed only to be expressed in S or M cones, and this study looks at the expression of GFP in vivo over time. This study marks the onset time of expression, and also shows that gene expression can be stable if a sufficiently high dose of viral vectors is given.
Mancuso et al. published their research in the journal: Nature in 2009, on converting squirrel mature dichromate monkeys into trichromats using gene therapy. New world monkeys such as squirrel monkeys do not have the L-opsin gene and are unable to distinguish between certain red and green colors. The researchers used recombinant AAV vectors to produce the human L-opsin gene into the monkey's retina. The cones acquiring lost genes begin to express new fotopigments.
The researchers raised two possibilities if therapy succeeded - that the monkeys would remain preoccupied with greater sensitivity to longer wavelengths of light, or they would be trichromats. Electroretinogram records show that they are able to distinguish blue-green from red-violet, and actually gain trichromation. The treated monkeys were also more successful when their color vision was tested with a modified Ishihara test.
In 2007, Alexander JJ et al. using gene therapy to restore some mouse sight with achromatopsia. The results were positive for 80% of the treated rats. In addition, a paper by KomÃÆ'¡romy et al., Published in 2010, deals with gene therapy for the form of achromatopsia in dogs. The function of cones and day vision has been restored for at least 33 months on two young dogs with achromatopsia. However, this therapy is less efficient for older dogs.
Theoretical questions
According to research by David H. Hubel and Torsten Wiesel, the suture of closing one eye of the monkey at an early age resulted in an irreversible vision loss in the eye, even after the stitches were removed. This study concludes that neural circuits for vision are transferred during "critical times" in childhood, after which the visual circuit can no longer be rewired to process new sensory inputs. Contrary to these findings, the success of Mancuso et al in providing tricky tricks to mature squirrel monkeys suggests that it is possible to adjust pre-existing sequences to allow for greater sharpness in color vision. The researchers concluded that integrating the stimulus of new photopigment as an adult was not analogous to loss of vision after visual deprivation.
Not yet known how animals that get new fotopigment feel new colors. While the article by Mancuso et al. stated that the monkeys actually acquired psychic tricks and gained the ability to distinguish between red and green, they claimed no knowledge of how animals internally feel the sensation.
While green/red blindness among deuteranopes can be treated by introducing the M-opsin genes, the more rare forms of color blindness such as tritanopia can in principle be treated as well. For tritanopia, the S-opsin gene should be introduced instead of the M-opsin gene.
Challenges
Despite success in animals, there are still challenges to perform gene therapy in humans to treat color blindness.
Security
How to transmit viral vectors to the retina may be a major obstacle to making gene therapy a practical treatment for color blindness. Because the virus must be injected directly by using a needle to penetrate the eye sclera, treatment may be very unpleasant and is a risk of eye infections. Without a way to give the virus noninvasively, treatment is somewhat risky for the benefits gained.
It is not yet known how often genes need to be injected to defend trick tricks among people who are color-blind congenitally. At the time of publication, Mancuso et al. reported that the squirrel monkey treated has maintained 2 years of color vision after treatment. If repeat injection is needed, there is also concern the body develops an immune response against the virus. If the body develops a sensitivity to the viral vector, the success of the therapy may be threatened and/or the body may respond poorly. An editorial by J. Bennett shows the use of Mancuso et al from "non-specific postinjectic corticosteroid therapy". Bennett points out that monkeys may be inflamed by injections. However, the common AAV virus used for this study is non-pathogenic, and the body is less likely to develop an immune response. Needless to say, an extensive review of the safety of care must precede human trials.
Subjects should first be evaluated to identify the required photopigment to get trick tricks. Also, while gene therapy can treat congenital color blindness (such as dichromacy), it is not intended to treat non-retinal color blind forms such as damage to the visual cortex of the brain.
Ethics
As a way of introducing new genetic information to change a person's phenotype, gene therapy for color blindness is open to the same ethical questions and criticisms as gene therapy in general. Given the large number of people with color blindness, there is also the question of whether color blindness is a nuisance. Furthermore, even if gene therapy successfully transforms incomplete individual color blinds into trichromates, the level of satisfaction among the subjects is unknown. It is uncertain how quality of life will improve (or worsen) after therapy.
See also
- Vivid color
- Achromatopsia
References
Source of the article : Wikipedia
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