出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2012/11/12 16:09:19」(JST)
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Retinitis Pigmentosa | |
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Classification and external resources | |
Fundus of patient with retinitis pigmentosa, mid stage (Bone spicule-shaped pigment deposits are present in the mid periphery along with retinal atrophy, while the macula is preserved although with a peripheral ring of depigmentation. Retinal vessels are attenuated.) From a review by Christian Hamel, 2006. |
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ICD-10 | H35.5 |
ICD-9 | 362.74 |
OMIM | 268000 |
MedlinePlus | 001029 |
MeSH | D012174 |
GeneReviews |
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Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment and often blindness.[1] Sufferers will experience one or more of the following symptoms:
The progress of RP is not consistent. Some people will exhibit symptoms from infancy, others may not notice symptoms until later in life.[2] Generally, the later the onset, the more rapid is the deterioration in sight. Also notice that people who do not have RP have 90 degree peripheral vision, while some people that have RP have less than 90 degree.
A form of retinal dystrophy, RP is caused by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina leading to progressive sight loss. Affected individuals may experience defective light to dark, dark to light adaptation or nyctalopia (night blindness), as the result of the degeneration of the peripheral visual field (known as tunnel vision). Sometimes, central vision is lost first causing the person to look sidelong at objects.
The effect of RP is best illustrated by comparison to a television or computer screen. The pixels of light that form the image on the screen equate to the millions of light receptors on the retina of the eye. The fewer pixels on a screen, the less distinct will be the images it will display. Fewer than 10 percent of the light receptors in the eye receive the colored, high intensity light seen in bright light or daylight conditions. These receptors are located in the center of the circular retina. The remaining 90 percent of light receptors receive gray-scale, low intensity light used for low light and night vision and are located around the periphery of the retina. RP destroys light receptors from the outside inward, from the center outward, or in sporadic patches with a corresponding reduction in the efficiency of the eye to detect light. This degeneration is progressive and has no known cure as of June 2012.
The most challenging aspect of RP is that it is not stable. Sufferers must continually adapt to less and less sight and how that impacts their life, career and relationships. Another aspect is that RP sufferers do not look different. RP does not result in any outward effect on the eyes and so people with RP "do not look blind". Furthermore, though legally blind because of reduced field of vision or acuity, they may be able to see things that hold in their line of sight long enough (if bright enough) to comprehend e.g. see large or bright objects albeit indistinctly.
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This section does not cite any references or sources. (June 2012) |
Mottling of the retinal pigment epithelium with black bone-spicule pigmentation is typically indicative (or pathognomonic) of retinitis pigmentosa. Other ocular features include waxy pallor of the optic nerve head, attenuation (thinning) of the retinal vessels, cellophane maculopathy, cystic macular edema and posterior subcapsular cataract.
This section does not cite any references or sources. (June 2012) |
The diagnosis of retinitis pigmentosa relies upon documentation of progressive loss in photoreceptor cell function by electroretinography (ERG) and visual field testing.
The mode of inheritance of RP is determined by family history. At least 35 different genes or loci are known to cause "nonsyndromic RP" (RP that is not the result of another disease or part of a wider syndrome).
DNA testing is available on a clinical basis for:
For all other genes (e.g. DHDDS), molecular genetic testing is available on a research basis only.
RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. X-linked RP can be either recessive, affecting primarily only males, or dominant, affecting both males and females, although males are usually more mildly affected. Some digenic (controlled by two genes) and mitochondrial forms have also been described.
Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing.
This section does not cite any references or sources. (June 2012) |
Retinitis pigmentosa (RP) is seen in a variety of diseases, so the differential of this sign alone is broad.
Other conditions include neurosyphilis, toxoplasmosis(Emedicine "Retinitis Pigmentosa") and Refsum's disease.
Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration.[3] This disorder is characterized by the progressive loss of photoreceptor cells and may eventually lead to blindness.[4]
There are multiple genes that, when mutated, can cause the Retinitis pigmentosa phenotype.[5] In 1989, a mutation of the gene for rhodopsin, a pigment that plays an essential part in the visual transduction cascade enabling vision in low-light conditions, was identified. Since then, more than 100 mutations have been found in this gene, accounting for 15% of all types of retinal degeneration. Most of those mutations are missense mutations and inherited mostly in a dominant manner.
Types include:
OMIM | Gene | Type |
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180100 | RP1 | Retinitis pigmentosa-1 |
312600 | RP2 | Retinitis pigmentosa-2 |
300029 | RPGR | Retinitis pigmentosa-3 |
608133 | PRPH2 | Retinitis pigmentosa-7 |
180104 | RP9 | Retinitis pigmentosa-9 |
180105 | IMPDH1 | Retinitis pigmentosa-10 |
600138 | PRPF31 | Retinitis pigmentosa-11 |
600105 | CRB1 | Retinitis pigmentosa-12, autosomal recessive |
600059 | PRPF8 | Retinitis pigmentosa-13 |
600132 | TULP1 | Retinitis pigmentosa-14 |
600852 | CA4 | Retinitis pigmentosa-17 |
601414 | HPRPF3 | Retinitis pigmentosa-18 |
601718 | ABCA4 | Retinitis pigmentosa-19 |
602772 | EYS | Retinitis pigmentosa-25 |
608380 | CERKL | Retinitis pigmentosa-26 |
607921 | FSCN2 | Retinitis pigmentosa-30 |
609923 | TOPORS | Retinitis pigmentosa-31 |
610359 | SNRNP200 | Retinitis pigmentosa 33 |
610282 | SEMA4A | Retinitis pigmentosa-35 |
610599 | PRCD | Retinitis pigmentosa-36 |
611131 | NR2E3 | Retinitis pigmentosa-37 |
268000 | MERTK | Retinitis pigmentosa-38 |
268000 | USH2A | Retinitis pigmentosa-39 |
612095 | PROM1 | Retinitis pigmentosa-41 |
612943 | KLHL7 | Retinitis pigmentosa-42 |
268000 | CNGB1 | Retinitis pigmentosa-45 |
613194 | BEST1 | Retinitis pigmentosa-50 |
613464 | TTC8 | Retinitis pigmentosa 51 |
613428 | C2orf71 | Retinitis pigmentosa 54 |
613575 | ARL6 | Retinitis pigmentosa 55 |
613617 | ZNF513 | Retinitis pigmentosa 58 |
613861 | DHDDS | Retinitis pigmentosa 59 |
613194 | BEST1 | Retinitis pigmentosa, concentric |
608133 | PRPH2 | Retinitis pigmentosa, digenic |
613341 | LRAT | Retinitis pigmentosa, juvenile |
268000 | SPATA7 | Retinitis pigmentosa, juvenile, autosomal recessive |
268000 | CRX | Retinitis pigmentosa, late-onset dominant |
300455 | RPGR | Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness |
The rhodopsin gene encodes a principal protein of photoreceptor outer segments. Studies show that mutations in this gene are responsible for approximately 25% of autosomal dominant forms of RP.[3][6]
Mutations in four pre-mRNA splicing factors are known to cause autosomal dominant retinitis pigmentosa. These are PRPF3 (human PRPF3 is HPRPF3; also PRP3), PRPF8, PRPF31 and PAP1. These factors are ubiquitously expressed and it is proposed that defects in a ubiquitous factor (a protein expressed everywhere) should only cause disease in the retina because the retinal photoreceptor cells have a far greater requirement for protein processing (rhodopsin) than any other cell type.[7]
Up to 150 mutations have been reported to date in the opsin gene associated with the RP since the Pro23His mutation in the intradiscal domain of the protein was first reported in 1990. These mutations are found throughout the opsin gene and are distributed along the three domains of the protein (the intradiscal, transmembrane, and cytoplasmic domains). One of the main biochemical causes of RP in the case of rhodopsin mutations is protein misfolding, and molecular chaperones have also been involved in RP.[8] It was found that the mutation of codon 23 in the rhodopsin gene, in which proline is changed to histidine, accounts for the largest fraction of rhodopsin mutations in the United States. Several other studies have reported other mutations which also correlate with the disease. These mutations include Thr58Arg, Pro347Leu, Pro347Ser, as well as deletion of Ile-255.[6][9][10][11][12] In 2000, a rare mutation in codon 23 was reported causing autosomal dominant retinitis pigmentosa, in which proline changed to alanine. However, this study showed that the retinal dystrophy associated with this mutation was characteristically mild in presentation and course. Furthermore, there was greater preservation in electroretinography amplitudes than the more prevalent Pro23His mutation.[13]
Currently there is no cure for retinitis pigmentosa, but treatments are now available in some countries. The progression of the disease can be reduced by the daily intake of 15000 IU (equivalent to 4.5 mg) of vitamin A palmitate in some patients.[14] Recent studies have shown that proper vitamin A supplementation can postpone blindness by up to 10 years (by reducing the 10% loss pa to 8.3% pa) in some patients in certain stages of the disease.[15] When it received market approval in February 2011, the Argus II retinal implant became the first approved treatment for the disease (CE Mark demonstrating safety and performance), and it is available in Germany, France, Italy, and UK. Interim results on 30 patients long term trials were published in Ophthalmology in 2012.
Future treatments may involve retinal transplants, artificial retinal implants,[16] gene therapy, stem cells, nutritional supplements, and/or drug therapies.
2006: Stem cells: UK Researchers working with mice, transplanted mouse stem cells which were at an advanced stage of development, and already programmed to develop into photoreceptor cells, into mice that had been genetically induced to mimic the human conditions of retinitis pigmentosa and age-related macular degeneration. These photoreceptors developed and made the necessary neural connections to the animal's retinal nerve cells, a key step in the restoration of sight. Previously it was believed that the mature retina has no regenerative ability. This research may in the future lead to using transplants in humans to relieve blindness.[17]
2008: Scientists at the Osaka Bioscience Institute have identified a protein, named Pikachurin, which they believe could lead to a treatment for retinitis pigmentosa.[18][19]
2010: A possible gene therapy seems to work in mice.[1]
2010: R-Tech Ueno (Japanese Medicine manufacture enterprise) completes phase II clinical study on ophthalmic solution UF-021 (Product Name Ocuseva (TM)) for Retinitis Pigmentosa
Also see Wikipedia entry on Tauroursodeoxycholic acid (TUDCA)
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リンク元 | 「tapetoretinal degeneration」「色素性網膜症」「rod-cone dystrophy」 |
関連記事 | 「pigmentary」 |
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