||This article may be too technical for most readers to understand. (October 2011)|
|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.
Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment and often blindness. The progress of RP is not consistent. Some people will exhibit symptoms from infancy, others may not notice symptoms until later in life. Generally, the later the onset, the more rapid is the deterioration in sight. Those 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.
Signs and symptoms
People may experience one or more of the following symptoms:
- Night blindness or nyctalopia;
- Tunnel vision (no peripheral vision);
- Peripheral vision (no central vision);
- Latticework vision;
- Aversion to glare;
- Slow adjustment from dark to light environments and vice versa;
- Blurring of vision;
- Poor color separation; and
- Extreme tiredness.
|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.
- RP combined with deafness (congenital or progressive) is called Usher syndrome.
- RP combined with opthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in the mitochondrial DNA disorder Kearns-Sayre syndrome (also known as Ragged Red Fiber Myopathy)
- RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, is absence of VLDL is seen in abetalipoproteinemia.
- RP is seen clinically in association with several other rare genetic disorders (including muscular dystrophy and chronic granulomatous disease) as part of McLeod syndrome. This is an X-linked recessive phenotype characterized by a complete absence of XK cell surface proteins, and therefore markedly reduced expression of all Kell red blood cell antigens. For transfusion purposes these patients are considered completely incompatible with all normal and K0/K0 donors.
Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration. This disorder is characterized by the progressive loss of photoreceptor cells and may eventually lead to blindness.
There are multiple genes that, when mutated, can cause the retinitis pigmentosa phenotype. 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.
|600105||CRB1||Retinitis pigmentosa-12, autosomal recessive|
|610359||SNRNP200||Retinitis pigmentosa 33|
|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|
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.
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. 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. 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.
|This section does not cite any references or sources. (June 2012)|
Retinitis pigmentosa (commonly referred to as "RP") is a disease characterised by loss of the light sensing photoreceptor cells that line the back of the eye, like the film of a camera. Usually the rod photoreceptors (responsible for night vision) are affected first, which is why loss of night vision (nyctalopia) is usually the first symptom. Loss of daytime vision (mediated by the cone photoreceptors) is usually preserved until the late stages of the disease. 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 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:
- RLBP1 (autosomal recessive, Bothnia type RP)
- RP1 (autosomal dominant, RP1)
- RHO (autosomal dominant, RP4)
- RDS (autosomal dominant, RP7)
- PRPF8 (autosomal dominant, RP13)
- PRPF3 (autosomal dominant, RP18)
- CRB1 (autosomal recessive, RP12)
- ABCA4 (autosomal recessive, RP19)
- RPE65 (autosomal recessive, RP20)
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.
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. 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. When it received market approval in February 2011, the Argus Retinal Prosthesis became the first approved treatment for the disease, and it is available in Germany, France, Italy, and UK. Operation of the prosthesis described here. Interim results on 30 patients long term trials were published in 2012.
The Argus II retinal implant has also received market approval in the USA. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities. In June 2013 12 hospitals in the USA announced to soon accept consultation for patients with RP in preparation for the launch of Argus II later that year.
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.
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
2012: Scientists at the Columbia University Medical Center showed on an animal model that gene therapy and induced pluripotent stem cell therapy may be viable options for treating retinits pigmentosa in the future.
Also see Wikipedia entry on Tauroursodeoxycholic acid (TUDCA)
- Derrick Morgan, Jamaican Ska, Rocksteady and Reggae superstar.
- Neil Fachie, British paralympic cyclist
- Lindy Hou, Australian tandem cyclist and triathlete
- Jon Wellner, American actor
- Steve Wynn, American business magnate and Las Vegas casino developer
- Rachael Leahcar, Australian Singer
- Matthew Benton, Caberet superstar and founder of the ' Matthew Benton dancers'
- Willie Brown, former Mayor of San Francisco
- Steve Lonegan, Mayor of Bogota, New Jersey, Republican candidate for US Senate
- Cone dystrophy
- Visual prosthetic
- List of eye diseases and disorders
- Retinal regeneration
- Progressive retinal atrophy for the condition in dogs
- Retinal degeneration (rhodopsin mutation)
- Adeno associated virus and gene therapy of the human retina
- "Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa".
- Koenekoop, R.K.; Loyer, Magali; Hand, Collette K; Al Mahdi, Huda; Dembinska, Olga; Beneish, Raquel; Racine, Julie; Rouleau, Guy A (2003). "Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families". American journal of ophthalmology 136 (4): 678–68. doi:10.1016/S0002-9394(03)00331-3.
- Hartong DT, Berson EL, Dryja TP (November 2006). "Retinitis pigmentosa". Lancet 368 (9549): 1795–809. doi:10.1016/S0140-6736(06)69740-7. PMID 17113430.
- Farrar GJ, Kenna PF, Humphries P (March 2002). "On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention". EMBO J. 21 (5): 857–64. doi:10.1093/emboj/21.5.857. PMC 125887. PMID 11867514.
- Online 'Mendelian Inheritance in Man' (OMIM) RETINITIS PIGMENTOSA; RP -268000
- Berson EL, Rosner B, Sandberg MA, Dryja TP (January 1991). "Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His)". Arch. Ophthalmol. 109 (1): 92–101. doi:10.1001/archopht.1991.01080010094039. PMID 1987956.
- Bujakowska, K.; Maubaret, C.; Chakarova, C. F.; Tanimoto, N.; Beck, S. C.; Fahl, E.; Humphries, M. M.; Kenna, P. F.; Makarov, E.; Makarova, O.; Paquet-Durand, F.; Ekstrom, P. A.; Van Veen, T.; Leveillard, T.; Humphries, P.; Seeliger, M. W.; Bhattacharya, S. S. (2009). "Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)". Investigative Ophthalmology & Visual Science 50 (12): 5927–5933. doi:10.1167/iovs.08-3275. PMID 19578015.
- Senin II, Bosch L, Ramon E, et al. (October 2006). "Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa". Biochem. Biophys. Res. Commun. 349 (1): 345–52. doi:10.1016/j.bbrc.2006.08.048. PMID 16934219.
- Dryja TP, McGee TL, Reichel E, et al. (January 1990). "A point mutation of the rhodopsin gene in one form of retinitis pigmentosa". Nature 343 (6256): 364–6. doi:10.1038/343364a0. PMID 2137202.
- Dryja TP, McGee TL, Hahn LB, et al. (November 1990). "Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa". N. Engl. J. Med. 323 (19): 1302–7. doi:10.1056/NEJM199011083231903. PMID 2215617.
- Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Dryja TP (May 1991). "Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347-leucine". Am. J. Ophthalmol. 111 (5): 614–23. PMID 2021172.
- Inglehearn CF, Bashir R, Lester DH, Jay M, Bird AC, Bhattacharya SS (January 1991). "A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa". Am. J. Hum. Genet. 48 (1): 26–30. PMC 1682750. PMID 1985460.
- Oh, Kean T.; Weleber, RG; Lotery, A; Oh, DM; Billingslea, AM; Stone, EM (1 September 2000). "Description of a New Mutation in Rhodopsin, Pro23Ala, and Comparison With Electroretinographic and Clinical Characteristics of the Pro23His Mutation". Archives of Ophthalmology 118 (9): 1269–76. doi:10.1001/archopht.118.9.1269. PMID 10980774.
- Berson, Eliot L.; Rosner, B; Sandberg, MA; Hayes, KC; Nicholson, BW; Weigel-DiFranco, C; Willett, W (1 June 1993). "A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa". Archives of Ophthalmology 111 (6): 761–72. doi:10.1001/archopht.1993.01090060049022. PMID 8512476.
- Berson EL (2007). "Long-term visual prognoses in patients with retinitis pigmentosa: the Ludwig von Sallmann lecture". Exp. Eye Res. 85 (1): 7–14. doi:10.1016/j.exer.2007.03.001. PMC 2892386. PMID 17531222.This is not verified by many Doctors
- Humayun, MS; Dorn, JD; da Cruz, L; Dagnelie, G; Sahel, JA; Stanga, PE; Cideciyan, AV; Duncan, JL; Eliott, D; Filley, E; Ho, AC; Santos, A; Safran, AB; Arditi, A; Del Priore, LV; Greenberg, RJ; Argus II Study, Group (2012 Apr). "Interim results from the international trial of Second Sight's visual prosthesis". Ophthalmology 119 (4): 779–88. doi:10.1016/j.ophtha.2011.09.028. PMC 3319859. PMID 22244176.
- "'First Bionic Eye' Retinal Chip for Blind". Science Daily. 29 June 2013. Retrieved 30 June 2013.
- "Ophthalmologists Implant Five Patients with Artificial Silicon Retina Microchip To Treat Vision Loss from Retinitis Pigmentosa" (Press release). Rush University Medical Center. 2005-01-31. Retrieved 2007-06-16.
- MacLaren, RE; RA Pearson, A MacNeil, RH Douglas, TE Salt, M Akimoto, A Swaroop, JC Sowden, RR Ali (2006-11-09). "Retinal repair by transplantation of photoreceptor precursors". Nature 444 (7116): 203–7. doi:10.1038/nature05161. PMID 17093405.
- Sato S, Omori Y, Katoh K, et al. (August 2008). "Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation". Nat. Neurosci. 11 (8): 923–931. doi:10.1038/nn.2160. PMID 18641643.
- Lightning-Fast Vision Protein Named After Pikachu July 24, 2008
- Experiments show retinitis pigmentosa is treatable December 22, 2012
- Neil Fachie http://www.paralympics.org.uk/gb/athletes/neil-fachie
- McDonald, Margie (31 May 2008). "Wheel turns a full circle as proud Lindy rides for two countries in Beijing". The Australian. p. 54. Retrieved 1 February 2012.
- "CSI Cast: Jon Wellner". CBS. Retrieved October 5, 2010.
- Paumgarten, Nick. "Doh! Dept: The $40-Million Elbow". The New Yorker. Retrieved 2012-08-13.
- Rizzo, Salvador. http://www.nj.com/politics/index.ssf/2013/09/lonegan_opens_up_about_his_blindness.html#incart_m-rpt-1. Missing or empty
- Retinitis pigmentosa at the Open Directory Project
- GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
- Patient support group for RP54 C2orf71 Retinitis Pigmentosa