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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Ilan Dock, B.S.;Jyostna Chouturi, M.B.B.S [2]
Overview
Retinitis may be caused by multiple infectious agents including cytomegalovirus, toxoplasmosis, tuberculosis, syphilis, and candida. Retinitis Pigmentosa is classified as a genetically predisposed eye disease which occurs as a result of an inherited genetic defect. [1]
Causes of Retinitis
Genetic
Retinitis Pigmentosa
- Retinitis Pigmentosa is classified as a genetically inherited eye disease, inherited from either one or both of a patient's parents. [2]
- The disease is a result of genetic defects in one of 50 genes required for the proper creation of photoreceptor proteins. [1]
- Generally the genetic disorder is linked to the inheritance of a recessive gene contributed by both parents. [2]
- Other cases have been linked to the inheritance of a dominant gene, defects of the X chromosome, and newly formed mutations caused by diseases.
- Progression of RP causes photoreceptor, cellular breakdown, of both rods and cones.
- Ultimately, the progressive breakdown of photoreceptors leads to restricted vision or permanent loss of vision. [2]
Retinitis Pigmentosa Genetics
- Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration.[3]
- There are multiple genes that, when mutated, can cause the retinitis pigmentosa phenotype.[4]
- 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.[5]
Defects in the Rhodopsin Gene
- The rhodopsin gene encodes a principal protein of photoreceptor outer segments.
- Mutations in this gene most commonly present as missense mutations or improper folding of the rhodopsin protein, and most frequently follow autosomal dominant inheritance patterns.
- Since the discovery of the rhodopsin gene, more than 100 RHO mutations have been identified, accounting for 15% of all types of retinal degeneration, and approximately 25% of autosomal dominant forms of RP.[3][6]
- Up to 150 mutations have been reported to date in the opsin gene associated with the RP.
- These mutations are found throughout the opsin gene and are distributed along the three domains of the protein (the intradiscal, transmembrane, and cytoplasmic domains).
- Two of the main biochemical causes of RP, in the case of rhodopsin mutations, are improper protein folding and the disruption of molecular chaperones.[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 various codon mutations associated with Retinitis Pigmentosa, including Thr58Arg, Pro347Leu, Pro347Ser, as well as deletion of Ile-255.[6][8][9][10][11]
- In 2000, a rare mutation in codon 23, in which proline changed to alanine, was reported . The mutation resulted in an autosomal dominant form of retinitis pigmentosa. However, this study showed that the retinal dystrophy associated with this mutation was characteristically mild in clinical presentation as well as progression. Furthermore, there was greater preservation in electroretinography amplitudes than the more prevalent Pro23His mutation.[12]
Autosomal Recessive Inheritance Patterns
- Autosomal recessive inheritance patterns of RP have been identified in at least 45 genes.[5]
- This means that two unaffected individuals who are carriers of the same RP-inducing gene mutation, in a diallelic form, can produce offspring with the RP phenotype.
- A mutation on the USH2A gene is known to cause 10-15% of a form of RP known as Usher's Syndrome, when inherited in an autosomal recessive fashion.[13]
- 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.
- The above factors are ubiquitously expressed.
- Defects in a ubiquitous factor (a protein expressed everywhere) usually cause disease in the retina due to the retinal photoreceptor cells far greater requirement for protein processing (rhodopsin) than any other cell type.[14]
- The somatic, or X-linked inheritance patterns of RP are currently identified with the mutations of six genes, the most common occurring at specific loci in the RPGR and RP2 genes.[13]
Retinitis Pigmentosa Genetic Defects
- Genetic defects and their associated retinitis pigmentosa subtypes are listed in the table below:
| 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 |
Infectious Agents
Cytomegalovirus Retinitis
- Cytomegalovirus retinitis is a result of a viral, herpes infection of the retina.
- Highly prevalent as a cause of blindness within the AIDS infected population.[15]
Syphilis
- Retinitis resulting from a syphilitic infection is commonly referred to as a ocular syphilis.
- The infection persists as syphilitic spirochetes, Treponema pallidum, invade or cause allergic reactions within the surrounding tissue.[15]
Fungal Infections
- Two types of retina infections may occur depending on the mode of fungal infection. These two types our outlined as endogenous or exogenous.
- Endogenous fungal retinitis is primarily a result of a disseminated fungal infection.
- Exogenous fungal infections primarily occur as a result of a recent event such as physical injury or surgery.
- Exogenous fungal infections are usually a result of Candidal retinitis. An infection commonly associated with candida chorioretinitis.
- Candidas chorioretinitis is typically caused by the species Candida albicans.[15]
Tuberculosis
- Extrapulmonary clinical manifestations of tuberculosis include intraocular, caseating granulomas.
- Infection of the retina is associated with the spread of the tuberculosis causing bacterial agents.
- Common presentation of tuberculosis in the retina appears as multiple choroidal tubercles.
- These tubercles are best defined as minor nodules with a grayish appearance.[15]
Toxoplasmosis
- Toxoplasma gondii is a parasitic agent found in contaminated meat and egg products.
- Persistence occurs within the vacuoles of cells found within tissues throughout the host.
- Rupturing of tissue cysts within host cells may lead to the progression of the disease, ultimately resulting in retinitis. This occurrence is mostly common within individuals who were previously immuno-compromised.[15]
References
- ↑ 1.0 1.1 Retinitis Pigmentosa. U.S. National Library of Medicine. https://www.genome.gov/13514348
- ↑ 2.0 2.1 2.2 Retinitis Pigmentosa. U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/ency/article/001029.htm
- ↑ 3.0 3.1 Hartong, Dyonne T; Berson, Eliot L; Dryja, Thaddeus P (2006). "Retinitis pigmentosa". The Lancet. 368 (9549): 1795–1809. doi:10.1016/S0140-6736(06)69740-7.
- ↑ Online Mendelian Inheritance in Man (OMIM) RETINITIS PIGMENTOSA; RP -268000
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 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.
- ↑ 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. line feed character in
|first5=at position 6 (help); line feed character in|first8=at position 6 (help); line feed character in|first7=at position 8 (help); line feed character in|title=at position 64 (help) - ↑ 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. doi:10.1016/s0002-9394(14)73708-0. 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.
- ↑ 13.0 13.1 http://ghr.nlm.nih.gov/condition/retinitis-pigmentosa[full citation needed]
- ↑ 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.
- ↑ 15.0 15.1 15.2 15.3 15.4 Infectious Retinitis: A Review. YACHNA AHUJA, MD · STEVEN M. COUCH, MD · RAYMUND R. RAZONABLE, MD · SOPHIE J. BAKRI, MD. http://www.retinalphysician.com/articleviewer.aspx?articleID=102293. Accessed April 13, 2016.