Rhodopsin

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Rhodopsin is a type of pigment, which is necessary for normal vision, particularly in low-light conditions. Rhodopsin is found in specialised cells called Rods which are located at the retina in the light-sensitive area of the eye. The rhodopsin structure is composed of scotopsin and 11 cis-retinal. Under the prevalence of light, 11 cis retinal dissociates from scotopsin and forms all-trans retinal[1]. Rhodopsin in the state forms intermediate compounds and eventually undergoes its formation of metarhodopsin (activated rhodopsin). At this stage, electrical impulses are sent to the brain as an interpretation of light.

Rhodopsin is very light sensitive and will photobleach when exposed to light[2].

Rhodopsin is the photoreceptor protein in rod cells of vertebrate retina[3]. It is also known as opsin 2.

Rhodopsin is a protein of 348 amino acids,has 7 transmembranal domains and is a member of the GPCR family, which is coupled to the G-protein: transducin. Rhodopsin, unlike many other GPCRs, is activated by a photon of light and not by the binding of a ligand. In fact, the ligand (11-cis retinal) is already bound in its inactive state. The photon causes a conformational change in the GPCR which causes activation of the transducin, of which the α subunit activates cyclic GMP phosphodiesterase[4]. Rhodopsin has an approved gene symbol of RHO and its cytogenetic location is marked at 3q22.1.

There are three mutations in the rhodopsin genes, two of which are transition mutations occurring at separate nucleotides of codon 347 and one transversion mutation occurring at codon 58. The two transition mutations involve C changing to T causing the codons to change to TCG and CTG from CCG. The transversion mutation involves C changing to G[5]. The third mutation is the replacement of a Threonine with Arginine in transmembrane spanning domain 1. The protein rhodopsin contains 20 Prolines. The Proline in position 23 is reported to be highly conserved and upon mutation can lead to the condition Retinitis Pigmentosa[6].

"Retinitis Pigmentosa" is an inherited disease that causes blindness or stationary night blindness, by degenerating retina cells. It might be an autosomal dominant or recessive and X-linked recessive disease, at which a mutation in the gene encoding rhodopsin. Vitamin A improves the condition[7][8]. Vitamin A is found naturally in many foods. A variety of meat and fish contain the useful vitamin, along with vegetables such as Carrots which contain large amounts of Beta Carotene. It was suggested, in Hum Mol Genet (2014)[9], that "many rhodopsin mutations are due to incorrect disulphide bond formation between C185 and C187 causing misfolding in the P23H rod opsin."

By somatic cell hybrid studies, Nathans et al. (1986) assigned the human rhodopsin gene to chromosome 3q21-qter.

Retinitis Pigmentosa

Retinitis Pigmentosa is a disease often linked with early-onset cystoid macular edema associated with the p.P347L mutation in the gene coding for Rhodopsin. Mutation in this gene can also cause congenital stationary night blindness[10].

A family of people, all sufferers of Retinitis Pigmentosa and all of whom have the p.P347L mutation in RHO, took part in an experiment to prove the link between these conditions. The participants were a 44-year-old mother, her two daughters aged 17 and 15, and two sons aged 13 and 11. A number of experimental techniques used to determine the functionality and anatomy of the retina were performed upon all of the family members, these included Funduscopy, Goldmann perimetry, spectral domain optical coherence tomography and electroretinogram.

The results of the spectral domain optical coherence tomography showed foveal atrophy in the case of the mother, she also showed poor visual acuity of light perception in both eyes. The results of the Funduscopy in the cases of the four children showed nothing out of the ordinary, however, the spectral domain optical coherence tomography showed they all had bilateral cystoid macular edema, and the electroretinogram showed the children had decreased cone response and no rod response at all.

The conclusion drawn from these experiments was that there is a strong possibility that cystoid macular edema in patients with Retinitis Pigmentosa could be linked to the p.P347L gene mutation within the rhodopsin gene. Further experiments on more patients with Retinitis Pigmentosa would be needed in order to confirm this[11][12].

Another experiment took part in Spain to find a correlation between mutations of RHO gene and Retinitis Pigmentisa. After 23 years of data collection. Overall 42 of 200 Spanish had mutated RHO gene. Looking at the data of 107 patients, p.Pro347Leu mutation which was seen on 4.5% of the subjects seemed to be the most prevalent and therefore was associated with the early onset and severe course diffuse Retinitis Pigmentosa[13].

It is suggested that vitamin A is beneficial in treating this condition. Vitamin A can be found in a range of food sources containing beta-carotene[14].

X-linked congenital stationary night blindness

X-linked congenital stationary night blindness is a disorder of the retina which leads to problems with vision in low levels of light. It is caused due to the mutation of the light detecting cells on the surface of the retina, the rods and cones. Two types of the disease are present, the Complete form, caused due to the mutation of gene NYX the Incomplete form due to mutations in gene CACNA1F. The NYX gene normally encodes a leucine-rich peptidoglycan, this mutation is a more frequent cause of congenital stationary blindness than the mutation of the CACNA1F gene[15].

References

  1. National Center for Biotechnology Information. PubChem Compound Database; https://pubchem.ncbi.nlm.nih.gov/compound/5280490, (2004)(accessed Oct. 20, 2015).
  2. Rhodopsin and the eye. 2016. Rhodopsin and the eye. [ONLINE] Available at: http://www.chm.bris.ac.uk/webprojects2003/rogers/998/Rhoeye.htm. [Accessed 20 October 2016].
  3. Hargrave P.A., McDowell J.H.(1992) Rhodopsin and phototransduction: a model system for G protein-linked receptors. The FASEB Journal, 6(6), 2323-2331
  4. Alberts.B, Johnson.A, Lewis.J, Raff.M, Roberts.K, Walter.P, 2008, Molecular Biology of the Cell, 5th Edition, New York, Garland Science
  5. Dryja TP et al (1990) Mutations in rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990 Nov 8;323(19):1302-7.
  6. Kelly J. (2011) Rhodopsin, Online Mendelian Inheritance in Man, http://omim.org/entry/180380, 1966 (accessed 18 Oct 2016)
  7. Kelly, J, (2011) Retinitis Pigmentosa 4; RP4,OMIM.org (last visited 20/11/2011)
  8. Thaddeus P. Dryja, M.D., Terri L. McGee, B.A., Lauri B. Hahn, M.S., et al. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med 1990; 323:1302-1307.
  9. Athanasiou D, Bevilacqua D, Aguila M, McCulley C, Kanuga N, Iwawaki T, Paul Chapple J, Cheetham ME, Hum Mol Genet. 2014 Dec 15;23(24):6594-606
  10. Human Mol. Genet. 1 (1), 41-45 (1992)
  11. Kim C, Chung H, Yu HG. (June 2012). Association of p.P347L in the rhodopsin gene with early-onset cystoid macular edema in patients with retinitis pigmentosa . 2 (33), 96-99.
  12. Kim C, Chung H, Yu HG. (June 2012). Association of p.P347L in the rhodopsin gene with early-onset cystoid macular edema in patients with retinitis pigmentosa.. . 2 (33), 96-99
  13. Acta Ophthalmol. 2015 Feb;93(1):e38-44. doi: 10.1111/aos.12486. Epub 2014 Nov 18
  14. Rhodopsin https://en.wikipedia.org/wiki/Rhodopsin 18 October 2017
  15. Allen L.E., Zito I., Bradshaw K., et al., 2003, Genotype-phenotype correlation in British families with X linked congenital stationary night blindness, Br J Ophthalmol, 87(11):1413-20
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