Retinitis pigmentosa
 | This article may be too technical for most readers to understand. (October 2011) |
| Retinitis pigmentosa | |
|---|---|
| Specialty | Ophthalmology  |
Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment and blindness.[1] Sufferers will experience one or more of the following symptoms:
- Night blindness nyctalopia;
- Tunnel vision (no peripheral vision);
- Peripheral vision (no central vision);
- Laticcework vision;
- Aversion to glare;
- Slow adjustment from dark to light environments and vice versa;
- Blurring of vision;
- Poor colour separation; and
- Extreme tiredness.
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.
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 affect of RP is best illustrated by comparison to a television or computer screen. The pixels o light that form the image on the screen equate to the millions of light receptors on the retina of the eye. The less pixels on a screen, the less distinct will be the images it will display. Less than 10 percent of all light receptors in the eye receive color, high intensity, light used 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 aroud 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 at 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.
Pathology
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.
Diagnosis
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:
- 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)
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.
Associated Conditions
Retinitis pigmentosa 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 (aka Ragged Red Fiber Myopathy)
- RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, is absence of VLDL is seen in abetalipoproteinemia.
Other conditions include neurosyphilis, toxoplasmosis(Emedicine "Retinitis Pigmentosa") and Refsum's disease.
Genetics
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 |
|---|---|---|
| Template:OMIM2 | RP1 | Retinitis pigmentosa-1 |
| Template:OMIM2 | RP2 | Retinitis pigmentosa-2 |
| Template:OMIM2 | RPGR | Retinitis pigmentosa-3 |
| Template:OMIM2 | PRPH2 | Retinitis pigmentosa-7 |
| Template:OMIM2 | RP9 | Retinitis pigmentosa-9 |
| Template:OMIM2 | IMPDH1 | Retinitis pigmentosa-10 |
| Template:OMIM2 | PRPF31 | Retinitis pigmentosa-11 |
| Template:OMIM2 | CRB1 | Retinitis pigmentosa-12, autosomal recessive |
| Template:OMIM2 | PRPF8 | Retinitis pigmentosa-13 |
| Template:OMIM2 | TULP1 | Retinitis pigmentosa-14 |
| Template:OMIM2 | CA4 | Retinitis pigmentosa-17 |
| Template:OMIM2 | HPRPF3 | Retinitis pigmentosa-18 |
| Template:OMIM2 | ABCA4 | Retinitis pigmentosa-19 |
| Template:OMIM2 | EYS | Retinitis pigmentosa-25 |
| Template:OMIM2 | CERKL | Retinitis pigmentosa-26 |
| Template:OMIM2 | FSCN2 | Retinitis pigmentosa-30 |
| Template:OMIM2 | TOPORS | Retinitis pigmentosa-31 |
| Template:OMIM2 | SNRNP200 | Retinitis pigmentosa 33 |
| Template:OMIM2 | SEMA4A | Retinitis pigmentosa-35 |
| Template:OMIM2 | PRCD | Retinitis pigmentosa-36 |
| Template:OMIM2 | NR2E3 | Retinitis pigmentosa-37 |
| Template:OMIM2 | MERTK | Retinitis pigmentosa-38 |
| Template:OMIM2 | USH2A | Retinitis pigmentosa-39 |
| Template:OMIM2 | PROM1 | Retinitis pigmentosa-41 |
| Template:OMIM2 | KLHL7 | Retinitis pigmentosa-42 |
| Template:OMIM2 | CNGB1 | Retinitis pigmentosa-45 |
| Template:OMIM2 | BEST1 | Retinitis pigmentosa-50 |
| Template:OMIM2 | TTC8 | Retinitis pigmentosa 51 |
| Template:OMIM2 | C2orf71 | Retinitis pigmentosa 54 |
| Template:OMIM2 | ARL6 | Retinitis pigmentosa 55 |
| Template:OMIM2 | ZNF513 | Retinitis pigmentosa 58 |
| Template:OMIM2 | DHDDS | Retinitis pigmentosa 59 |
| Template:OMIM2 | BEST1 | Retinitis pigmentosa, concentric |
| Template:OMIM2 | PRPH2 | Retinitis pigmentosa, digenic |
| Template:OMIM2 | LRAT | Retinitis pigmentosa, juvenile |
| Template:OMIM2 | SPATA7 | Retinitis pigmentosa, juvenile, autosomal recessive |
| Template:OMIM2 | CRX | Retinitis pigmentosa, late-onset dominant |
| Template:OMIM2 | 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 still a puzzle as to why defects in a ubiquitous factor should only cause disease in the retina.
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.[7] 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][8][9] [10] [11] 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.[12]
Treatment
Currently there is no treatment for retinitis pigmentosa. 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.[13] 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.[14]
Research on possible treatments
Future treatments may involve retinal transplants, artificial retinal implants,[15] 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.[16]
2008: Scientists at the Osaka Bioscience Institute have identified a protein, named Pikachurin, which they believe could lead to a treatment for retinitis pigmentosa.[17][18]
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 TUDCA
Notable people with RP
- Sue Arnold, Anglo-Burmese UK based journalist
- Richard H. Bernstein, American lawyer, triathlon athlete, and rights advocate for the visually impaired
- Willie Brown, American politician and former Mayor of San Francisco
- Viviane Forest, Canadian Paralympic alpine skier
- Gordon Gund, U.S. sports team owner
- Lindy Hou, Australian tandem cyclist and triathlete [19]
- Sheena Iyengar, American academic
- Ryan Knighton, Canadian writer
- Jim Knipfel, American novelist, autobiographer, and journalist
- Amar Latif Scottish entrepreneur, television actor, director and motivational speaker
- Dave Kelly Founder and managing director of disability charity, Daisy Inclusive UK
- Isaac Lidsky, former child actor and first blind US Supreme Court clerk
- Tony Sarre, Australian filmmaker
- Woody Shaw, American jazz musician
- Amanda Swafford, American model and America's Next Top Model contestant
- John Totleben, American illustrator
- Rigo Tovar, Mexican singer, composer, and songwriter
- Mildred Weisenfeld, founder of the Fight for Sight eye research foundation in 1946.
- Jon Wellner, American actor[20]
- Steve Wynn, American business magnate and Las Vegas casino developer[21]
- Helgi Hjörvar, icelandic member of parliament for the social democratic alliance
- Teigan Van Roosmalen, Australian Paralympian
- Derrick Morgan, Jamaican Ska, Rocksteady and Reggae Musician.
- Rachael Leahcar, Australian singer and The Voice Australia contestant
See also
- Cone dystrophy
- Visual prosthetic
- List of eye diseases and disorders
- Progressive retinal atrophy for the condition in dogs
- Retinal degeneration (rhodopsin mutation)
- Adeno associated virus and gene therapy of the human retina
References
- ^ a b "Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa".
- ^ Koenekoop, R.K. (2003). Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families. American journal of ophthalmology 136(4), pp. 678-68
- ^ a b Hartong DT, Berson EL, Dryja TP (2006). "Retinitis pigmentosa". Lancet. 368 (9549): 1795–809. doi:10.1016/S0140-6736(06)69740-7. PMID 17113430.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Farrar GJ, Kenna PF, Humphries P (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Online Mendelian Inheritance in Man (OMIM): RETINITIS PIGMENTOSA; RP - 268000
- ^ a b Berson EL, Rosner B, Sandberg MA, Dryja TP (1991). "Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His)". Arch. Ophthalmol. 109 (1): 92–101. PMID 1987956.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Senin II, Bosch L, Ramon E; et al. (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.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Dryja TP, McGee TL, Reichel E; et al. (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.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Dryja TP, McGee TL, Hahn LB; et al. (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.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Dryja TP (1991). "Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347-leucine". Am. J. Ophthalmol. 111 (5): 614–23. PMID 2021172.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Inglehearn CF, Bashir R, Lester DH, Jay M, Bird AC, Bhattacharya SS (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Oh KT, Weleber RG, Lotery A, Oh DM, Billingslea AM, Stone EM (2000). "Description of a new mutation in rhodopsin, Pro23Ala, and comparison with electroretinographic and clinical characteristics of the Pro23His mutation". Arch. Ophthalmol. 118 (9): 1269–76. PMID 10980774.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Berson EL, Rosner B, Sandberg MA; et al. (1993). "A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa". Arch. Ophthalmol. 111 (6): 761–72. PMID 8512476.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ 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
- ^ "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 (2006-11-09). "Retinal repair by transplantation of photoreceptor precursors". Nature. 444 (7116): 203–7. doi:10.1038/nature05161. PMID 17093405.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Sato S, Omori Y, Katoh K; et al. (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.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Lightning-Fast Vision Protein Named After Pikachu July 24, 2008
- ^ 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.
- ^ http://www.newyorker.com/archive/2006/10/23/061023ta_talk_paumgarten