Retinitis pigmentosa 350926 220591832 2008-06-20T16:33:15Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{DiseaseDisorder infobox | Name = Retinitis pigmentosa | ICD10 = {{ICD10|H|35|5|h|30}} | ICD9 = {{ICD9|362.74}} | OMIM = 268000 | MeshID = D012174 }} [[Image:Human eyesight two children and ball normal vision.jpg|thumb|right|220ppx|Normal vision. Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]]]] [[Image:Human eyesight two children and ball with retinitis pigmentosa or tunnel vision.png|thumb|right|220px|The same view with tunnel vision from retinitis pigmentosa. The blackness surrounding the central image does not indicate darkness, but rather a lack of perceived visual information.]] '''Retinitis pigmentosa''' ('''RP''') is a group of genetic [[eye]] conditions. In the progression of symptoms for RP, [[nyctalopia|night blindness]] generally precedes [[tunnel vision]] by years or even decades. Many people with RP do not become legally [[blindness|blind]] until their 40s or 50s and retain some sight all their life. Others go completely blind from RP, in some cases as early as childhood. Progression of RP is different in each case. RP is a type of hereditary retinal [[dystrophy]], a group of inherited disorders in which abnormalities of the [[photoreceptors]] ([[rod cell|rod]]s and [[cone cell|cone]]s) or the [[retinal pigment epithelium]] (RPE) of the [[retina]] lead to progressive visual loss. Affected individuals first experience defective dark adaptation or [[nyctalopia]] (night blindness), followed by reduction of the [[peripheral vision|peripheral visual field]] (known as tunnel vision) and, sometimes, loss of central vision late in the course of the disease. ==Signs== 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, [[maculopathy|cellophane maculopathy]], [[cystic]] macular [[edema]] and [[cataract|posterior subcapsular cataract]]. ==Diagnosis== The [[diagnosis]] of retinitis pigmentosa relies upon documentation of progressive loss in [[photoreceptor]] function by [[electroretinography]] (ERG) and [[visual field]] testing. The mode of [[inheritance]] of RP is determined by family history. At least 35 different [[gene]]s 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: * {{Gene|RLBP1}} (autosomal recessive, Bothnia type RP) * {{Gene|RP1}} (autosomal dominant, RP1) * {{Gene|RHO}} (autosomal dominant, RP4) * {{Gene|RDS}} (autosomal dominant, RP7) * {{Gene|PRPF8}} (autosomal dominant, RP13) * {{Gene|PRPF3}} (autosomal dominant, RP18) * {{Gene|CRB1}} (autosomal recessive, RP12) * {{Gene|ABCA4}} (autosomal recessive, RP19) * {{Gene|RPE65}} (autosomal recessive, RP20) For all other genes, molecular [[genetic testing]] is available on a research basis only. RP can be inherited in an [[autosomal dominant]], [[autosomal recessive]], or [[Sex linkage|X-linked]] manner. X-linked RP can be either [[recessive]], affecting primarily only males, or [[dominant allele|dominant]], affecting both males and females, although females 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. RP combined with progressive deafness is called [[Usher syndrome]]. ==Genetics== Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal [[Degenerative disease|degeneration]]. <ref>Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18; 368(9549): 1795-809.</ref> This disorder is characterized by the progressive loss of [[photoreceptor]] cells and may eventually lead to blindness. <ref>Farrar GJ, Kenna PF, Humphries P. On the genetics of retinitis pigmentosa and on mutation- independent approaches to therapeutic intervention. EMBO J. 2002; 21:857–864.</ref> There are multiple [[genes]] that, when mutated, can cause the Retinitis pigmentosa [[phenotype]]. <ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=268000 |title=OMIM - RETINITIS PIGMENTOSA; RP |accessdate=2007-09-22 |format= |work=}}</ref> In 1989, a [[mutation]] of the gene for [[rhodopsin]], a [[pigment]] that plays an essential part in the [[Signal transduction|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 mutation]]s and inherited mostly in a [[dominant allele|dominant]] manner. The rhodopsin gene [[Coding strand|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 <ref>Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18; 368(9549): 1795-809. </ref><ref>Berson EL, Rosner B, Sandberg MA, Dryja TP. Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His). Arch Ophthalmol. 1991;109:92-101. </ref>. 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]] [[Protein domain|domains]]). One of the main biochemical causes of RP in the case of rhodopsin mutations is [[protein folding|protein misfolding]], and [[molecular chaperones]] have also been involved in RP <ref>Ivan I. Senin, Laia Bosch, Eva Ramon, Evgeni Yu. Zernii, Joan Manyosa, Pavel P. Philippov, and Pere Garriga. Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa. Biochemical and Biophysical Research Communications. Volume 349, Issue 1, 13 October 2006, Pages 345-352. </ref>. 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 <ref>TP, McGee TL, Reichel E, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990; 343:364-366. </ref><ref>Dryja TP, McGee TL, Hahn LB, et al. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990;323:1302-1307. </ref><ref>Berson EL, Rosner B, Sandberg MA, Dryja TP. Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His). Arch Ophthalmol. 1991;109:92-101. </ref><ref>Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Dryja TP. Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347- leucine. Am J Ophthalmol. 1991;111:614-623. </ref><ref>Inglehearn, C. F., Bashir, R., Lester, D. H., Jay, M., Bird, A. C. & Bhattacharya,- S. S. (1991) Am. J. Hum. Genet. 48, 26-30. </ref>. 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]] [[amplitude]]s than the more prevalent Pro23His mutation <ref>Kean T. Oh, MD; Richard G. Weleber, MD; Andrew Lotery, MD, FRCOphth; Dawn M. Oh, MS; Andrea M. Billingslea, BS; Edwin M. Stone, MD, PhD. Description of a New Mutation in Rhodopsin, Pro23Ala, and Comparison With Electroretinographic and Clinical Characteristics of the Pro23His Mutation, Arch Ophthalmol. 2000; 118:1269-1276. </ref>. ==Other causes== Some cases of RP are part of a wider syndrome, or come about a result of other diseases such as: * [[Fahr disease]] * [[Bardet-Biedl syndrome]] * [[Lowe syndrome]] * [[Usher's syndrome]] * [[Subacute necrotising encephalomyelopathy]] * [[Pyruvate carboxylase deficiency]] * [[MELAS]] * [[Hereditary sensory-motor neuropathy type 7]] * [[Rud's syndrome]] * [[Refsum's disease]] * [[Kearns-Sayre syndrome]] * [[Carbohydrate deficient glycoprotein syndrome type 1a]] * [[Loken Senior syndrome]] * [[Hallervorden-Spatz disease]] * [[Abetalipoproteinaemia]] * [[Homocarnosinase deficiency]] * [[Mirhosseini-Holmes-Walton syndrome]] * [[Shwachman-Diamond syndrome]] * [[HARP syndrome]] * [[Alström syndrome]] * [[Medullary cystic renal disease]] * [[Stargardt's disease]] * [[Sjogren-Larsson syndrome]] * [[Tapetochoroidal dystrophy]] ==Treatment== There is currently no medical treatment that can completely cure retinitis pigmentosa, although the progression of the disease can be reduced by the daily intake of 15000 IU of [[vitamin A]] palmitate.<ref name="pmid8512476">{{cite journal |author=Berson EL, Rosner B, Sandberg MA, ''et al'' |title=A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa |journal=Arch. Ophthalmol. |volume=111 |issue=6 |pages=761–72 |year=1993 |pmid=8512476 |doi=}}</ref> Recent studies have shown that proper vitamin A supplementation can postpone blindness by up to 10 years.<ref name="pmid17531222">{{cite journal |author=Berson EL |title=Long-term visual prognoses in patients with retinitis pigmentosa: the Ludwig von Sallmann lecture |journal=Exp. Eye Res. |volume=85 |issue=1 |pages=7–14 |year=2007 |pmid=17531222 |doi=10.1016/j.exer.2007.03.001}}</ref> Scientists continue to investigate possible treatments. Future treatments may involve retinal [[organ transplant|transplant]]s, artificial retinal [[implant]]s,<ref>{{cite press release | title = Ophthalmologists Implant Five Patients with Artificial Silicon Retina Microchip To Treat Vision Loss from Retinitis Pigmentosa | publisher = [[Rush University]] Medical Center | date = [[2005-01-31]] | url = http://www.rush.edu/webapps/MEDREL/servlet/NewsRelease?ID=608 | accessdate = 2007-06-16 }}</ref> [[gene therapy]], [[stem cell]]s, [[Dietary supplement|nutritional supplements]], and/or [[Pharmacology|drug therapies]]. In a study published in the journal [[Nature (journal)|Nature]], researchers working with mice at the [[University College London]] Institutes of [[Ophthalmology]] and Child Health and [[Moorfields Eye Hospital]], transplanted mouse [[stem cells]] which were at an advanced stage of development, and already programmed to develop into [[photoreceptor]]s, 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.<ref> {{cite journal | last = MacLaren | first = RE | coauthors = RA Pearson, A MacNeil, RH Douglas, TE Salt, M Akimoto, A Swaroop, JC Sowden, RR Ali | date = [[2006-11-09]] | title = Retinal repair by transplantation of photoreceptor precursors | journal = [[Nature]] | volume = 444 | issue = 7116 | pages = 203–207 | pmid = 17093405 | doi = 10.1038/nature05161 }}</ref> ==See also== *[[Cone dystrophy]] *[[Visual prosthetic]] *[[List of eye diseases and disorders]] *[[Progressive retinal atrophy]] for the condition in dogs ==References== {{reflist}} ==External links== {{Spoken Wikipedia|Retinitis_pigmentosa.ogg|2006-02-17}} *[http://www.amdsupport.ca/articles/61/1/Electronic-Implant-in-the-Eye-Restores-Sight-of-Two-Patients-Suffering-from-Retinitis-Pigmentosa/Page1.html Retinal Implants Restore Vision] *[http://www.foresightrp.com/ Foresight, a Dubai-based charity fighting to find a cure for blindness caused by hereditary eye disease, particularly Retinitis Pigmentosa] *[http://www.brps.org.uk/ The British Retinitis Pigmentosa Society] *[http://news.bbc.co.uk/2/hi/health/7359282.stm BBC News - Bionic eye 'blindness cure hope'] *[http://www.retina.org.nz/ Retina New Zealand] *[http://www.nlm.nih.gov/medlineplus/ency/article/001029.htm Retinitis Pigmentosa] (Medline Plus). *[http://merritew.tripod.com/retinitispigmentosa More about Retinitis Pigmentosa] *[http://www.exploratorium.edu/seeing/notfadeaway/ Not Fade Away] &mdash; one man's journey into blindness (Exploratorium) *[http://news.com.com/2102-11390_3-6057581.html?tag=st.util.print Retinal implants may soon restore lost vision] *[http://www.bostonretinalimplant.org/ The Boston Retinal Implant Project] *[http://groups.yahoo.com/group/RP-Friends/ The '''RP-Friends''' Mailing List is a discussion group where people with Retinitis Pigmentosa gather for friendship & support.] *[http://www.retinitispigmentosa.net/forum Retinitis Pigmentosa Forum] *[http://www.muhc.ca/media/news/?ItemID=22109 Breakthrough by MUHC researcher has major implications for diagnosis, treatment of childhood blindness] *[http://www.blindness.org/ The Foundation Fighting Blindness] *[http://www.aetmis.gouv.qc.ca/site/index.php?en_publications_2006 Visual Mobility Aids for Patients with Night Blindness (AETMIS 06-09)] Agence d’évaluation des technologies et des modes d’intervention en santé (AETMIS). [[Montreal]] December 2006 *[http://www.rpsa.org.za/ Retina South Africa] *[http://rp.zeno.pl/ Polish discussion forum for Patients with Retinitis Pigmentosa] {{Eye pathology}} [[Category:genetic disorders]] [[Category:Ophthalmology]] [[Category:Channelopathy]] [[Category:Blindness]] [[ar:العشى الليلي]] [[bs:Retinitis pigmentosa]] [[de:Retinopathia pigmentosa]] [[es:Retinosis pigmentaria]] [[fr:Rétinite pigmentaire]] [[it:Retinite pigmentosa]] [[he:רטיניטיס פיגמנטוזה]] [[nl:Retinitis pigmentosa]] [[ja:網膜色素変性症]] [[no:Retinitis pigmentosa]] [[pl:Retinopatia barwnikowa]] [[pt:Retinite pigmentosa]] [[fi:Verkkokalvorappeuma]] [[sv:Retinitis pigmentosa]] [[zh:視網膜色素變性]]