Main Article Content

Abstract

Vision process involves the participation of two types of retinal photoreceptor cells: rod cells respond to dim light while cone cells respond to bright light and colours. The visual pigments in both types of photoreceptor cells contain the common chromophore, 11-cis-retinal, linked through a Schiff base linkage to the opsin protein, a member of G-protein coupled receptor (GPCR) family, composed of 7-transmembrane helices (a 7TM receptor). Rhodopsin is the visual pigment present in the rod cells while three distinct types of visual pigments known as photopsins (red cones, green cones and blue cones absorbing red, blue and green parts of the visible spectrum respectively) are present in the cone cells. Absorption of light by the visual pigment causes the photoexcitation followed by photoisomerization, 11-cis-retinal (Z) to all-trans-retinal (E) with a high quantum yield through a number of reactive intermediates characterized by low temperature and picosecond (ps) time resolved spectroscopies coupled with femtosecond spectroscopy. This photoisomerization leads to a change in the conformation of opsin GPCR and a signal transduction cascade by activating transducin, a heterotrimeric G-protein, to breakdown the cGMP to close the cGMP-gated cation channels resulting in hyperpolarization of the photoreceptor cell. This action potential creates a nerve signal that is transmitted to the brain to produce the sense of vision. The photoisomerized pigment undergoes rapidly hydrolysis to produce the opsin protein and all trans-retinal, which can be reconverted enzymatically to 11-cis-retinal for recharging opsin to generate the active visual pigment to maintain the vision cycle (Wald cycle). This brief review highlights the state of our understanding of the biology behind the art of vision in humans and other organisms.

Keywords

Vitamin A 11-cis-Retinal All-trans-retinal Photoisomerization Opsin Rhodopsin Photopsins G-protein coupled receptor Trnsducin RPE65 Wald’s visual cycle.

Article Details

How to Cite
Das1, A., Das, U., & K. Das, A. (2023). Present State of Knowledge of Chemistry of Our Vision: Photoreceptor Molecules and Vision Cycle. Asian Journal of Organic & Medicinal Chemistry, 7(4), 309–320. https://doi.org/10.14233/ajomc.2022.AJOMC-P408

References

  1. G. Wald, The Molecular Basis of Visual Excitation, Nature, 219, 800 (1968); https://doi.org/10.1038/219800a0
  2. R.R. Rando, The Biochemistry of the Visual Cycle, Chem. Rev., 101, 1881 (2001); https://doi.org/10.1021/cr960141c
  3. H. Kandori, Y. Shichida and T. Yoshizawa, Photoisomerization in Rhodopsin, Biochemistry, 66, 1197 (2001); https://doi.org/10.1023/A:1013123016803
  4. S.O. Smith, Structure and Activation of the Visual Pigment Rhodopsin, Annu. Rev. Biophys., 39, 309 (2010); https://doi.org/10.1146/annurev-biophys-101209-104901
  5. B. Jastrzebska, Y. Tsybovsky and K. Palczewski, Complexes between Photoactivated Rhodopsin and Transducin: Progress and Questions, Biochem. J., 428, 1 (2010); https://doi.org/10.1042/BJ20100270
  6. O.P. Ernst, D.T. Lodowski, M. Elstner, P. Hegemann, L.S. Brown and H. Kandori, Microbial and Animal Rhodopsins: Structures, Functions, and Molecular Mechanisms, Chem. Rev., 114, 126 (2014); https://doi.org/10.1021/cr4003769
  7. P.D. Kiser, M. Golczak and K. Palczewski, Chemistry of the Retinoid (Visual) Cycle, Chem. Rev., 114, 194 (2014); https://doi.org/10.1021/cr400107q
  8. F. Gonzalez-Fernandez, B. Betts-Obregon, B. Yust, J. Mimun, D. Sung, D. Sardar and A.T. Tsin, Interphotoreceptor Retinoid-Binding Protein Protects Retinoids from Photodegradation, Photochem. Photobiol., 91, 371 (2015); https://doi.org/10.1111/php.12416
  9. C. Schnedermann, X. Yang, M. Liebel, K.M. Spillane, J. Lugtenburg, I. Fernández, A. Valentini, I. Schapiro, M. Olivucci, P. Kukura and R.A. Mathies, Evidence for a Vibrational Phase-Dependent Isotope Effect on the Photochemistry of Vision, Nat. Chem., 10, 449 (2018); https://doi.org/10.1038/s41557-018-0014-y
  10. A. Morshedian, J.J. Kaylor, S.Y. Ng, A. Tsan, R. Frederiksen, T. Xu, L. Yuan, A.P. Sampath, R.A. Radu, G.L. Fain and G.H. Travis, Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells, Neuron, 102, 1172 (2019); https://doi.org/10.1016/j.neuron.2019.04.004
  11. J. Zhang, E.H. Choi, A. Tworak, D. Salom, H. Leinonen, C.L. Sander, T.V. Hoang, J.T. Handa, S. Blackshaw, G. Palczewska, P.D. Kiser and K. Palczewski, Photic Generation of 11-cis-Retinal in Bovine Retinal Pigment Epithelium, J. Biol. Chem., 294, 19137 (2019); https://doi.org/10.1074/jbc.RA119.011169
  12. E.H. Choi, A. Daruwalla, S. Suh, H. Leinonen and K. Palczewski, Retinoids in the Visual Cycle: Role of the Retinal G Protein-Coupled Receptor, J. Lipid Res., 62, 100040 (2021); https://doi.org/10.1194/jlr.TR120000850
  13. P.D. Kiser, M. Golczak, A. Maeda and K. Palczewski, Key Enzymes of the Retinoid (Visual) Cycle in Vertebrate Retina, Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1821, 137 (2012); https://doi.org/10.1016/j.bbalip.2011.03.005
  14. A.K. Das, M. Das and A. Das, Biophysical, Bioinorganic & Bioinorganic Chemistry, Books & Allied (P) Ltd.: Kolkata, India, Edn. 2 (2021). ISBN: 978-81-948455-2-2.
  15. U. Satyanaryana, Biochemistry, Books & Allied (P) Ltd.: Kolkata, India, Edn. 2 (2002). ISBN: 81-87134-80-1
  16. T. Ebrey and Y. Koutalos, Vertebrate Photoreceptors, Prog. Retin. Eye Res., 20, 49 (2001); https://doi.org/10.1016/S1350-9462(00)00014-8
  17. D. Mustafi, A.H. Engel and K. Palczewski, Structure of Cone Photoreceptors, Prog. Retin. Eye Res., 28, 289 (2009); https://doi.org/10.1016/j.preteyeres.2009.05.003
  18. M. Yang and H.K.W. Fong, Synthesis of the All-trans-Retinal Chromophore of Retinal G Protein-coupled Receptor Opsin in Cultured Pigment Epithelial Cells, J. Biol. Chem., 277, 3318 (2002); https://doi.org/10.1074/jbc.M108946200
  19. J.K. Bowmaker and H.J. Dartnall, Visual Pigments of Rods and Cones in a Human Retina, J. Physiol., 298, 501 (1980); https://doi.org/10.1113/jphysiol.1980.sp013097
  20. A. Tsin, B. Betts-Obregon and J. Grigsby, Visual Cycle Proteins: Structure, Function and Roles in Human Retinal Disease, J. Biol. Chem., 293, 13016 (2018); https://doi.org/10.1074/jbc.AW118.003228
  21. K. Palczewski and P.D. Kiser, Shedding New Light on the Generation of the Visual Chromophore, Proc. Natl. Acad. Sci. USA, 117, 19629 (2020); https://doi.org/10.1073/pnas.2008211117
  22. J.M. Berg, J.L. Tymoczko and L. Stryer, Biochemistrty, W.H. Freeman and Company: New York, Edn. 7 (2012),
  23. V.Y. Arshavsky, T.D. Lamb and E.N. Pugh Jr., G Proteins and Phototransduction, Annu. Rev. Physiol., 64, 153 (2002); https://doi.org/10.1146/annurev.physiol.64.082701.102229
  24. K. Palczewski, T. Kumasaka, T. Hori, C.A. Behnke, H. Motoshima, B.A. Fox, I.L. Trong, D.C. Teller, T. Okada, R.E. Stenkamp, M. Yamamoto and M. Miyano, Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor, Science, 289, 739 (2000); https://doi.org/10.1126/science.289.5480.739
  25. K. Palczewski, G Protein–Coupled Receptor Rhodopsin, Annu. Rev. Biochem., 75, 743 (2006); https://doi.org/10.1146/annurev.biochem.75.103004.142743
  26. X.E. Zhou, K. Melcher and H.E. Xu, Structure and Activation of Rhodopsin, Acta Pharmacol. Sin., 33, 291 (2012); https://doi.org/10.1038/aps.2011.171
  27. G. Wald and R. Hubbard, The Synthesis of Rhodopsin from Vitamin A1, Proc. Natl. Acad. Sci. USA, 36, 92 (1950); https://doi.org/10.1073/pnas.36.2.92
  28. R. Kawaguchi, J. Yu, J. Honda, J. Hu, J. Whitelegge, P. Ping, P. Wiita, D. Bok and H. Sun, A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A, Science, 315, 820 (2007); https://doi.org/10.1126/science.1136244
  29. J.C. Saari, Vitamin A Metabolism in Rod and Cone Visual Cycles, Annu. Rev. Nutr., 32, 125 (2012); https://doi.org/10.1146/annurev-nutr-071811-150748
  30. J.C. Saari, Eds.: M. Asson-Batres and C. Rochette-Egly, Vitamin A and Vision, The Biochemistry of Retinoid Signaling II; In: Subcellular Biochemistry, Springer, Dordrecht, vol. 81, p. 231 (2016); https://doi.org/10.1007/978-94-024-0945-1_9
  31. H. Tsukamoto and A. Terakita, Diversity and Functional Properties of Bistable Pigments, Photochem. Photobiol. Sci., 9, 1435 (2010); https://doi.org/10.1039/c0pp00168f
  32. D. Osorio and M. Vorobyev, Photoreceptor Sectral Sensitivities in Terrestrial Animals: Adaptations for Luminance and Colour Vision, Proc. R. Soc. B Biol. Sci., 272, 1745 (2005); https://doi.org/10.1098/rspb.2005.3156
  33. T. Mizukami, H. Kandori, Y. Shichida, A.H. Chen, F. Derguini, C.G. Caldwell, C.F. Biffe, K. Nakanishi and T. Yoshizawa, Photoisomerization Mechanism of the Rhodopsin Chromophore: Picosecond Photolysis of Pigment Containing 11-cis-Locked Eight-Membered Ring Retinal, Proc. Natl. Acad. Sci. USA, 90, 4072 (1993); https://doi.org/10.1073/pnas.90.9.4072
  34. J. Clayden, N. Greeves and S. Warren, Organic Chemistry, Oxford University Press, Edn. 2 (2012). ISBN: 978-0-19-927029-3.
  35. H.J.A. Dartnall, The Photosensitivities of Visual Pigments in the Presence of Hydroxylamine, Vision Res., 8, 339 (1968); https://doi.org/10.1016/0042-6989(68)90104-1
  36. R. Frederiksen, S. Nymark, A.V. Kolesnikov, J.D. Berry, L. Adler IV, Y. Koutalos, V.J. Kefalov and M.C. Cornwall, Rhodopsin Kinase and Arrestin Binding Control the Decay of Photoactivated Rhodopsin and Dark Adaptation of Mouse Rods, J. Gen. Physiol., 148, 1 (2016); https://doi.org/10.1085/jgp.201511538
  37. T.D. Lamb and E.N. Pugh Jr., Dark Adaptation and the Retinoid Cycle of Vision, Prog. Retin. Eye Res., 23, 307 (2004); https://doi.org/10.1016/j.preteyeres.2004.03.001
  38. A. Muniz, E.T. Villazana-Espinoza, A.L. Hatch, S.G. Trevino, D.M. Allen and A.T. Tsin, A Novel Cone Visual Cycle in the Cone-dominated Retina, Exp. Eye Res., 85, 175 (2007); https://doi.org/10.1016/j.exer.2007.05.003
  39. A. Muñiz, W.A. Greene, M.L. Plamper, J.H. Choi, A.J. Johnson, A.T. Tsin and H.C. Wang, Retinoid Uptake, Processing, and Secretion in Human iPS-RPE Support the Visual Cycle, Invest. Ophthalmol. Vis. Sci., 55, 198 (2014); https://doi.org/10.1167/iovs.13-11740
  40. A. Muniz, B.S. Betts, A.R. Trevino, K. Buddavarapu, R. Roman, J.X. Ma and A.T. Tsin, Evidence for Two Retinoid Cycles in the Cone-Dominated Chicken Eye, Biochemistry, 48, 6854 (2009); https://doi.org/10.1021/bi9002937
  41. P. Ala-Laurila, A.V. Kolesnikov, R.K. Crouch, S.A. Shukolyukov, E. Tsina, V.I. Govardovskii, Y. Koutalos, B. Wiggert, M.E. Estevez and M.C. Cornwall, Visual Cycle: Dependence of Retinol Production and Removal on Photoproduct Decay and Cell Morphology, J. Gen. Physiol., 128, 153 (2006); https://doi.org/10.1085/jgp.200609557
  42. G. Wolf, The Visual Cycle of the Cone Photoreceptors of the Retina, Nutr. Rev., 62, 283 (2004); https://doi.org/10.1111/j.1753-4887.2004.tb00053.x
  43. J.S. Wang and V.J. Kefalov, The Cone-Specific Visual Cycle, Prog. Retin. Eye Res., 30, 115 (2011); https://doi.org/10.1016/j.preteyeres.2010.11.001
  44. G. Wolf, Function of the Protein Rpe65 in the Visual Cycle, Nutr. Rev., 63, 97 (2005); https://doi.org/10.1111/j.1753-4887.2005.tb00127.x
  45. P.D. Kiser and K. Palczewski, Membrane-Binding and Enzymatic Properties of RPE65, Prog. Retin. Eye Res., 29, 428 (2010); https://doi.org/10.1016/j.preteyeres.2010.03.002
  46. R.A. Radu, J. Hu, J. Peng, D. Bok, N.L. Mata and G.H. Travis, etinal Pigment Epithelium-Retinal G Protein Receptor-Opsin Mediates Light-dependent Translocation of All-trans-retinyl Esters for Synthesis of Visual Chromophore in Retinal Pigment Epithelial Cells, J. Biol. Chem., 283, 19730 (2008); https://doi.org/10.1074/jbc.M801288200
  47. M.L. Batten, Y. Imanishi, T. Maeda, D.C. Tu, A.R. Moise, D. Bronson, D. Possin, R.N. Van Gelder, W. Baehr and K. Palczewski, Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver, J. Biol. Chem., 279, 10422 (2004); https://doi.org/10.1074/jbc.M312410200
  48. A. Wenzel, V. Oberhauser, E.N. Pugh Jr., T.D. Lamb Jr., C. Grimm, M. Samardzija, E. Fahl, M.W. Seeliger, C.E. Reme and J. von Lintig, The Retinal G Protein-coupled Receptor (RGR) Enhances Isomerohydrolase Activity Independent of Light, J. Biol. Chem., 280, 29874 (2005); https://doi.org/10.1074/jbc.M503603200
  49. M. Jin, S. Li, W.N. Moghrabi, H. Sun and G.H. Travis, Rpe65 Is the Retinoid Isomerase in Bovine Retinal Pigment Epithelium, Cell, 122, 449 (2005); https://doi.org/10.1016/j.cell.2005.06.042
  50. G. Moiseyev, Y. Chen, Y. Takahashi, B. X. Wu and J. X. Ma, RPE65 is the Isomerohydrolase in the Retinoid Visual Cycle, Proc. Natl. Acad. Sci., (USA), 102, 12413 (2005); https://doi.org/10.1073/pnas.0503460102
  51. A.K. Das, M, Das and A. Das, Bioinorganic Chemistry, Books & Allied (P) Ltd, Kolkata, India, Edn. 2 (2020); ISBN: 978-81-946982-1-0.
  52. L. Hofmann and K. Palczewski, Advances in Understanding the Molecular Basis of the First Steps in Color Vision, Prog. Retin. Eye Res., 49, 46 (2015); https://doi.org/10.1016/j.preteyeres.2015.07.004
  53. G.H. Travis, M. Golczak, A.R. Moise and K. Palczewski, Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents, Annu. Rev. Pharmacol. Toxicol., 47, 469 (2007); https://doi.org/10.1146/annurev.pharmtox.47.120505.105225
  54. P.D. Kiser and K. Palczewski, Retinoids and Retinal Diseases, Annu. Rev. Vis. Sci., 2, 197 (2016); https://doi.org/10.1146/annurev-vision-111815-114407
  55. P.D. Kiser and K. Palczewski, Pathways and Disease-Causing Alterations in Visual Chromophore Production for Vertebrate Vision, J. Biol. Chem., 296, 100072 (2021); https://doi.org/10.1074/jbc.REV120.014405
  56. N. Gordon, Colour Blindness, Public Health, 112, 81 (1998); https://doi.org/10.1016/S0033-3506(98)00590-3
  57. M.F. Marmor, Vision, Eye Disease, and Art: 2015 Keeler Lecture, Eye, 30, 287 (2016); https://doi.org/10.1038/eye.2015.197
  58. D.M. Hunt, K.S. Dulai, J.K. Bowmaker and J.D. Mollon, The Chemistry of John Dalton's Color Blindness, Science, 267, 984 (1995); https://doi.org/10.1126/science.7863342