||This article may be too technical for most readers to understand. (October 2011)|
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.
|Classification and external resources|
|Patient UK||Retinitis pigmentosa|
Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment  due to the progressive degeneration of the rod photoreceptor cells in the retina. This form of retinal dystrophy manifests initial symptoms independent of age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. Patients in the early stages of RP first notice compromised peripheral and dim light vision due to the decline of the rod photoreceptors  The progressive rod degeneration is later followed by abnormalities in the adjacent retinal pigment epithelium (RPE) and the deterioration of cone photoreceptor cells. As peripheral vision becomes increasingly compromised, patients experience progressive "tunnel vision" and eventual blindness. Affected individuals may additionally experience defective light-dark adaptations, nyctalopia (night blindness), and the accumulation of bone spicules in the fundus (eye).
The initial retinal degenerative symptoms of Retinitis Pigmentosa are characterized by decreased night vision (nyctalopia) and the loss of the mid-peripheral visual field. The rod photoreceptor cells, which are responsible for low-light vision and are orientated in the retinal periphery, are the retinal processes affected first during non-syndromic forms of this disease. Visual decline progresses relatively quickly to the far peripheral field, eventually extending into the central visual field as tunnel vision increases. Visual acuity and color vision can become compromised due to accompanying abnormalities in the cone photoreceptor cells, which are responsible for color vision, visual acuity, and sight in the central visual field. The progression of disease symptoms occurs in a symmetrical manner, with both the left and right eyes experiencing symptoms at a similar rate.
A variety of indirect symptoms characterize Retinitis Pigmentosa along with the direct affects of the initial rod photoreceptor degeneration and later cone photoreceptor decline. Phenomena such as photophobia, which describes the event in which light is perceived as an intense glare, and photopsia, the presence of blinking or shimmering lights within the visual field, often manifest during the later stages of RP. Findings related to RP have often been characterized in the fundus (eye) of the eye as the Ophthalamic triad. This includes the development of a mottled appearance of the retinal pigment epithelium (RPE) caused by bone spicule formation, a waxy appearance of the optic nerve, and the attentuation of blood vessels in the retina.
Non-syndromic RP usually presents a variety of the following symptoms:
- Night blindness or nyctalopia;
- Tunnel vision (due to loss of peripheral vision);
- Latticework vision;
- Photopsia (blinking/shimmering lights);
- Photophobia (Aversion to glare);
- Development of bone spicules in the fundus;
- Slow adjustment from dark to light environments and vice versa;
- Blurring of vision;
- Poor color separation;
- Loss of central vision;
- Eventual blindness
Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration. There are multiple genes that, when mutated, can cause the retinitis pigmentosa phenotype. Inheritance patterns of RP have been identified as autosomal dominant, autosomal recessive, X-linked, and maternally (mitochondrially) acquired , and are dependent on the specific RP gene mutations present in the parental generation. 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|
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.
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.
Autosomal recessive inheritance patterns of RP have been identified in at least 45 genes. This means that two unaffected individuals who are carriers of the same RP-inducing gene mutation in diallelic form can produce offspring with the RP phenotype. A mutation on the USH2A gene is known to cause 10-15% of a syndromic form of RP known as Usher's Syndrome when inherited in an autosomal recessive fashion.
Animal models suggest that the retinal pigment epithelium fails to phagocytose the outer rod segment discs that have been shed, leading to an accumulation of outer rod segment debris. In mice that are homozygous recessive for retinal degeneration mutation, rod photoreceptors stop developing and undergo degeneration before cellular maturation completes. A defect in cGMP-phosphodiesterase has also been documented; this leads to toxic levels of cGMP.
|This section does not cite any references or sources. (June 2012)|
RP may be: (1) Non-syndromic, that is, it occurs alone, without any other clinical findings, (2) Syndromic, with other neurosensory disorders, developmental abnormalities, or complex clinical findings, or (3) Secondary to other systemic diseases.
- RP combined with deafness (congenital or progressive) is called Usher syndrome.
- RP combined with ophthalmoplegia, 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.
- RP associated with hypogonadism, and developmental delay with an autosomal recessive inheritance pattern is seen with Laurence-Moon-Bardet-Biedl syndrome
|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. 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.
2012: Scientists at the University of Miami Bascom Palmer Eye Institute presented data showing protection of photoreceptors in an animal model when eyes were injected with mesencephalic astrocyte-derived neurotrophic factor (MANF).
2014: A study conducted by the University of Alicante in Spain indicated that the cannabinoids from marijuana may slow vision loss in cases of Retinitis Pigmentosa.
Researchers at the University of California, Berkeley were able to restore vision to blind mice by exploiting a "photoswitch" that activates retinal ganglion cells in specimen with damaged rod and cone cells.
Also see Wikipedia entry on Tauroursodeoxycholic acid (TUDCA)
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- 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
- Busskamp, V.; Duebel, J.; Balya, D.; Fradot, M.; Viney, T. J.; Siegert, S.; Groner, A. C.; Cabuy, E.; Forster, V.; Seeliger, M.; Biel, M.; Humphries, P.; Paques, M.; Mohand-Said, S.; Trono, D.; Deisseroth, K.; Sahel, J. A.; Picaud, S.; Roska, B. (2010). "Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa". Science 329 (5990): 413–7. Bibcode:2010Sci...329..413B. doi:10.1126/science.1190897. PMID 20576849.
- Koenekoop, Robert 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): 678–87. doi:10.1016/S0002-9394(03)00331-3. PMID 14516808.
- http://www.kellogg.umich.edu/patientcare/downloads/Understand-Retinitis-Pigmentosa.pdf[full citation needed]
- Farrar, G.J.; Kenna, P. F.; Humphries, P (2002). "NEW EMBO MEMBer's REVIEW: On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention". The EMBO Journal 21 (5): 857–64. doi:10.1093/emboj/21.5.857. PMC 125887. PMID 11867514.
- Shintani, Kelly; Shechtman, Diana L.; Gurwood, Andrew S. (2009). "Review and update: Current treatment trends for patients with retinitis pigmentosa". Optometry 80 (7): 384–401. doi:10.1016/j.optm.2008.01.026. PMID 19545852.
- Soucy, E; Wang, Y; Nirenberg, S; Nathans, J; Meister, M (1998). "A Novel Signaling Pathway from Rod Photoreceptors to Ganglion Cells in Mammalian Retina". Neuron 21 (3): 481–93. doi:10.1016/S0896-6273(00)80560-7. PMID 9768836.
- Hartong, Dyonne T; Berson, Eliot L; Dryja, Thaddeus P (2006). "Retinitis pigmentosa". The Lancet 368 (9549): 1795. doi:10.1016/S0140-6736(06)69740-7.
- Online 'Mendelian Inheritance in Man' (OMIM) RETINITIS PIGMENTOSA; RP -268000
- Rivolta, C.; Sharon, D; Deangelis, M. M.; Dryja, T. P. (2002). "Retinitis pigmentosa and allied diseases: Numerous diseases, genes, and inheritance patterns". Human Molecular Genetics 11 (10): 1219–27. doi:10.1093/hmg/11.10.1219. PMID 12015282.
- Berson, Eliot L.; Rosner, B; Sandberg, M. A.; Dryja, T. P. (1991). "Ocular Findings in Patients with Autosomal Dominant Retinitis Pigmentosa and a Rhodopsin Gene Defect (Pro-23-His)". Archives of Ophthalmology 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. doi:10.1167/iovs.08-3275.
- Senin, Ivan I.; Bosch, Laia; Ramon, Eva; Zernii, Evgeni Yu.; Manyosa, Joan; Philippov, Pavel P.; Garriga, Pere (2006). "Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa". Biochemical and Biophysical Research Communications 349 (1): 345–52. doi:10.1016/j.bbrc.2006.08.048. PMID 16934219.
- Dryja, Thaddeus P.; McGee, Terri L.; Reichel, Elias; Hahn, Lauri B.; Cowley, Glenn S.; Yandell, David W.; Sandberg, Michael A.; Berson, Eliot L. (1990). "A point mutation of the rhodopsin gene in one form of retinitis pigmentosa". Nature 343 (6256): 364–6. Bibcode:1990Natur.343..364D. doi:10.1038/343364a0. PMID 2137202.
- Dryja, Thaddeus P.; McGee, Terri L.; Hahn, Lauri B.; Cowley, Glenn S.; Olsson, Jane E.; Reichel, Elias; Sandberg, Michael A.; Berson, Eliot L. (1990). "Mutations within the Rhodopsin Gene in Patients with Autosomal Dominant Retinitis Pigmentosa". New England Journal of Medicine 323 (19): 1302–7. doi:10.1056/NEJM199011083231903. PMID 2215617.
- Berson, E. L.; Rosner, B; Sandberg, M. A.; Weigel-Difranco, C; Dryja, T. P. (1991). "Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347-leucine". American journal of ophthalmology 111 (5): 614–23. PMID 2021172.
- Inglehearn, C. F.; Bashir, R; Lester, D. H.; Jay, M; Bird, A. C.; Bhattacharya, S. S. (1991). "A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa". American journal of human genetics 48 (1): 26–30. PMC 1682750. PMID 1985460.
- Oh, Kean T.; Weleber, R. G.; Lotery, A; Oh, D. M.; Billingslea, A. M.; Stone, E. M. (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.
- http://ghr.nlm.nih.gov/condition/retinitis-pigmentosa[full citation needed]
- Daiger, S P; Sullivan, L S; Bowne, S J (2013). "Genes and mutations causing retinitis pigmentosa". Clinical Genetics 84 (2): 132–41. doi:10.1111/cge.12203. PMC 3856531. PMID 23701314.
- Berson, Eliot L.; Rosner, B; Sandberg, M. A.; Hayes, K. C.; Nicholson, B. W.; Weigel-Difranco, C; Willett, W (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, Eliot L. (2007). "Long-term visual prognoses in patients with retinitis pigmentosa: The Ludwig von Sallmann lecture". Experimental Eye Research 85 (1): 7–14. doi:10.1016/j.exer.2007.03.001. PMC 2892386. PMID 17531222.
- http://2-sight.eu/ee/how-does-argus-ii-produce-sight[full citation needed]
- Humayun, Mark S.; Dorn, Jessy D.; Da Cruz, Lyndon; Dagnelie, Gislin; Sahel, José-Alain; Stanga, Paulo E.; Cideciyan, Artur V.; Duncan, Jacque L.; Eliott, Dean; Filley, Eugene; Ho, Allen C.; Santos, Arturo; Safran, Avinoam B.; Arditi, Aries; Del Priore, Lucian V.; Greenberg, Robert J.; Argus Ii Study, Group (2012). "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.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm339824.htm[full citation needed]
- "'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, R. E.; Pearson, R. A.; MacNeil, A.; Douglas, R. H.; Salt, T. E.; Akimoto, M.; Swaroop, A.; Sowden, J. C.; Ali, R. R. (2006). "Retinal repair by transplantation of photoreceptor precursors". Nature 444 (7116): 203–7. Bibcode:2006Natur.444..203M. doi:10.1038/nature05161. PMID 17093405.
- Sato, Shigeru; Omori, Yoshihiro; Katoh, Kimiko; Kondo, Mineo; Kanagawa, Motoi; Miyata, Kentaro; Funabiki, Kazuo; Koyasu, Toshiyuki; Kajimura, Naoko; Miyoshi, Tomomitsu; Sawai, Hajime; Kobayashi, Kazuhiro; Tani, Akiko; Toda, Tatsushi; Usukura, Jiro; Tano, Yasuo; Fujikado, Takashi; Furukawa, Takahisa (2008). "Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation". Nature Neuroscience 11 (8): 923–31. 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
- http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=76ea053d-6fdd-4338-ac0b-66e2ff1885a1&cKey=a6522c99-616b-4978-8252-b8dff363a98e&mKey=f0fce029-9bf8-4e7c-b48e-9ff7711d4a0e[full citation needed]
- http://www.medicaljane.com/2014/02/17/spanish-study-cannabis-may-help-delay-retinal-degeneration-vision-loss/[full citation needed]
- Tochitsky, Ivan; Polosukhina, Aleksandra; Degtyar, Vadim E.; Gallerani, Nicholas; Smith, Caleb M.; Friedman, Aaron; Van Gelder, Russell N.; Trauner, Dirk; Kaufer, Daniela; Kramer, Richard H. (2014). "Restoring Visual Function to Blind Mice with a Photoswitch that Exploits Electrophysiological Remodeling of Retinal Ganglion Cells". Neuron 81 (4): 800–13. doi:10.1016/j.neuron.2014.01.003. PMC 3933823. PMID 24559673.
- 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
- "Interview with Metro Online". Retrieved September 4, 2006.
- Retinitis pigmentosa at DMOZ
- GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
- Patient support group for RP54 C2orf71 Retinitis Pigmentosa