Retinitis pigmentosa

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Retinitis Pigmentosa
Fundus of patient with retinitis pigmentosa, mid stage.jpg
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
ICD-10 H35.5
ICD-9 362.74
OMIM 268000
MedlinePlus 001029
NCI Retinitis pigmentosa
Patient UK Retinitis pigmentosa
MeSH D012174

Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment and often blindness.[1] 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.[citation needed] Those who do not have RP have 90 degree peripheral vision, while some people who have RP have less than 90 degrees.

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.

Signs and symptoms[edit]

Normal vision.
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.

RP is characterized by the progressive loss of photoreceptor cells and may eventually lead to blindness.[3] 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.

Associated conditions[edit]

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. [4]

  • 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

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.[5] There are multiple genes that, when mutated, can cause the retinitis pigmentosa phenotype.[6] 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
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.[5][7]

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.[8]

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.[9] 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.[7][10][11][12][13] 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.[14]


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.


Retinitis pigmentosa (commonly referred to as "RP") is a disease characterized 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. 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.


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.


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.[15] 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.[16] 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.[17]

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.[18]


Future treatments may involve retinal transplants, artificial retinal implants,[19] 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.[20]

2008: Scientists at the Osaka Bioscience Institute have identified a protein, named Pikachurin, which they believe could lead to a treatment for retinitis pigmentosa.[21][22]

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

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.[23]

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).[24]

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. [25]

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.[26]

Also see Wikipedia entry on Tauroursodeoxycholic acid (TUDCA)

Notable cases[edit]

See also[edit]


  1. ^ a b "Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa". 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Daiger SP, Sullivan LS, Bowne SJ. Genes and mutations causing retinitis pigmentosa. Clin Genet 2013: 84: 132–141.
  5. ^ a b 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. 
  6. ^ Online 'Mendelian Inheritance in Man' (OMIM) RETINITIS PIGMENTOSA; RP -268000
  7. ^ a b 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. 
  8. ^ 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.  edit
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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
  17. ^ 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 (April 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. 
  18. ^ "'First Bionic Eye' Retinal Chip for Blind". Science Daily. 29 June 2013. Retrieved 30 June 2013. 
  19. ^ "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. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ Lightning-Fast Vision Protein Named After Pikachu July 24, 2008
  23. ^ Experiments show retinitis pigmentosa is treatable December 22, 2012
  24. ^ [1]
  25. ^
  26. ^
  27. ^ Neil Fachie
  28. ^ 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. 
  29. ^ "CSI Cast: Jon Wellner". CBS. Retrieved October 5, 2010. 
  30. ^ Paumgarten, Nick. "Doh! Dept: The $40-Million Elbow". The New Yorker. Retrieved 2012-08-13. 
  31. ^ Rizzo, Salvador.  Missing or empty |title= (help)
  32. ^ "Interview with Metro Online". Retrieved September 4, 2006. 

External links[edit]