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The role and evolutionary development of retinoic-acid signalling in the eye

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Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications

Part of the book series: MCBU Molecular and Cell Biology Updates ((MCBU))

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Abstract

From the earliest time of its discovery as an essential nutrient, vitamin A has been known to be vital for the eye, both for its development and for its adult function. In the mature organism, the earliest sign of vitamin A deficiency is night-blindness, and in the developing embryo vitamin A deficiency causes the ventral eye to be defective, leading to micro- or anophthalmia [1, 2]. Because the oxidation of retinaldehyde to retinoic acid (RA) is an irreversible reaction, it was possible to assay their biological roles separately [3]. These assays revealed that when adult rats are fed a diet completely lacking in vitamin A (retinol and β-carotene) and are given RA, they survive but turn blind due to photoreceptor degeneration. This illustrates the two distinct functions of the retinoids: 11-cis retinaldehyde forms the visual chromophore of rhodopsin, and RA regulates gene transcription throughout the body. In this brief review we will summarize evidence that these two functions, which are commonly studied in different fields of science, are connected in the eye. We discovered highly intricate expression patterns of different RA-generating aldehyde dehydrogenases in the developing and mature eye, and in the functioning eye we find that light causes an increase in RA. These observations indicate that the transcriptional role of RA may have its origin in vision.

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References

  1. Hale F (1937) The relation of maternal vitamin A deficiency to microphthalmia in pigs. Texas State J Med 33: 228–232

    Google Scholar 

  2. Warkany J, Schraffenberger E (1946) Congenital malformations induced in rats by maternal vitamin A deficiency. I. Defects of the eye. Arch Ophthalmol 35: 150–169

    Article  CAS  Google Scholar 

  3. Dowling JE, Wald G (1960) The biological function of vitamin A acid. Proc Nall Acad Sci USA 46: 587–608

    Article  CAS  Google Scholar 

  4. McCaffery P, Tempst P, Lara G, Dräger UC (1991) Aldehyde dehydrogenase is a positional marker in the retina. Development 112: 693–702

    PubMed  CAS  Google Scholar 

  5. Petersen D, Lindahl R (1997) Aldehyde dehydrogenases. In: FP Guengerich (ed): Comprehensive Toxicology: Biotransformations Vol 3. Pergamon Press, New York, 97–118

    Google Scholar 

  6. Holmes RS (1988) Alcohol dehydrogenases and aldehyde dehydrogenases of anterior eye tissues from humans and other mammals. In: K Kuriyama, A Takada, H Ishii (eds): Biomedical and Social Aspects of Alcohol and Alcoholism. Elsevier Science Publishers, Amsterdam, 51–57

    Google Scholar 

  7. Lee M-O, Manthey CL, Sladek NE (1991) Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. Biochem Pharmacol 42: 1279–1285

    Article  PubMed  CAS  Google Scholar 

  8. McCaffery P, Lee M-O, Wagner MA, Sladek NE, Dräger UC (1992) Asymmetrical retinoic acid synthesis in the dorso-ventral axis of the retina. Development 115: 371–382

    PubMed  CAS  Google Scholar 

  9. McCaffery M, Dräger UC (1997) A sensitive bioassay for enzymes that synthesize retinoic acid. Brain Res Protocols 1: 232–236

    Article  CAS  Google Scholar 

  10. Wagner M, Han B, Jessell TM (1992) Regional differences in retinoid release from embryonic neural tissue detected by an in vitro reporter assay. Development 116: 55–66

    PubMed  CAS  Google Scholar 

  11. McCaffery P, Posch KC, Napoli JL, Gudas L, Dräger UC (1993) Changing patterns of the retinoic acid system in the developing retina. Dev Biol 158: 390–399

    Article  CAS  Google Scholar 

  12. McCaffery P, Dräger UC (1993) Retinoic acid synthesis in the developing retina. Adv Exp Med Biol 328: 181–190

    Article  PubMed  CAS  Google Scholar 

  13. Dräger UC, McCaffery P (1997) Retinoic acid and development of the retina. Progr Retin Eye Res 16: 323–346

    Article  Google Scholar 

  14. Zhao D, McCaffery P, Ivins KJ, Neve RL, Hogan P, Chin WW, Dräger UC (1996) Molecular identification of a major retinoic-acid synthesizing enzyme: a retinaldehyde-specific dehydrogenase. Eur J Biochem 240: 15–22

    Article  PubMed  CAS  Google Scholar 

  15. Dräger UC, McCaffery P (1995) Retinoic-acid synthesis in the developing spinal cord. Adv Exp Med Biol 372: 185–192

    PubMed  Google Scholar 

  16. Niederreither K, McCaffery P, Dräger UC, Chambon P, Dollé P (1997) Restricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse development. Mech Develop 62: 67–78

    Article  CAS  Google Scholar 

  17. McCaffery P, Dräger UC (1994) Hotspots of retinoic acid synthesis in the developing spinal cord. Proc Nall Acad Sci USA 91: 7194–7197

    Article  CAS  Google Scholar 

  18. Yamamoto M, McCaffery P, Dräger UC (1996) Influence of the choroid plexus on cerebellar development: analysis of retinoic acid synthesis. Develop Brain Res 93: 182–190

    Article  CAS  Google Scholar 

  19. McCaffery P, Dräger UC (1994) High levels of a retinoic-acid generating dehydrogenase in the meso-telencephalic dopamine system. Proc Nail Acad Sci USA 91: 7772–7776

    Article  CAS  Google Scholar 

  20. Moss JB, Xavier-Neto J, Shapiro M, Nayeem M, McCaffery P, Dräger UC, Rosenthal N (1998) Dynamic patterns of retinoic acid synthesis and response in the developing mammalian heart. Dev Biol 199: 55–71

    Article  PubMed  CAS  Google Scholar 

  21. Yamamoto M, Dräger UC, McCaffery P (1998) A novel assay for retinoic acid catabolic enzymes shows high expression in the developing hindbrain. Develop Brain Res 107: 103–111

    Article  CAS  Google Scholar 

  22. Dollé P, Ruberte E, Leroy P, Morriss-Kay G, Chambon P (1990) Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogen-esis. Development 110: 1133–1151

    Google Scholar 

  23. Dollé P, Fraulob V, Kastner P, Chambon P (1994) Developmental expression of =tine retinoid X receptor (RXR) genes. Mech Develop 45: 91–104

    Article  Google Scholar 

  24. Simeone A, Acampora D, Arcioni L, Andrews PW, Boncinelli E, Mavilio F (1990) Sequential activation of Hox2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346: 763–766

    Article  PubMed  CAS  Google Scholar 

  25. Shenefelt RE (1972) Morphogenesis of malformations in hamsters caused by retinoic acid. Teratology 5: 403–418

    Article  Google Scholar 

  26. Marsh-Armstrong N, McCaffery P, Dowling JE, Gilbert W, Dräger UC (1994) Retinoic acid is necessary for development of the ventral retina in zebrafish. Proc Natl Acad Sci USA 91: 7286–7290

    Article  PubMed  CAS  Google Scholar 

  27. Hyatt GA, Schmitt EA, Marsh-Armstrong NA, Dowling JE (1992) Retinoic acid-induced duplication of the zebrafish retina. Proc Natl Acad Sci USA 89: 8293–8297

    Article  PubMed  CAS  Google Scholar 

  28. Hyatt G, Schmitt EA, Marsh-Armstrong N, McCaffery P, Dräger UC, Dowling JE (1996) Retinoic acid establishes ventral retinal characteristics. Development 122: 195–204

    PubMed  CAS  Google Scholar 

  29. Mathers PH, Grinberg A, Mahon KA, Jamrich M (1997) The Rx homeobox gene is essential for vertebrate eye development. Nature 387: 603–607

    Article  PubMed  CAS  Google Scholar 

  30. Li H, Tierney C, Wen L, Wu JY, Rao Y (1997) A single morphogenetic field gives rise to two retina primor-dia under the influence of the prechordal plate. Development 124: 603–615

    PubMed  CAS  Google Scholar 

  31. Quiring R, Walldorf U, Kloter U, Gehring WJ (1994) Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265: 785–789

    Article  PubMed  CAS  Google Scholar 

  32. Chiang C, Litingtung Y, Lee E, Young K, Corden J, Westphal H, Beachy P (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383: 407–413

    Article  PubMed  CAS  Google Scholar 

  33. McCaffery P, Mey J, Dräger UC (1996) Light-mediated retinoic acid production. Proc Natl Acad Sci USA 93: 12 570–12 574

    Google Scholar 

  34. Cahill GM, Besharse JC (1995) Circadian rhythmicity in vertebrate retinas: regulation by a photoreceptor oscillator. Progr Retin Eye Res 14: 267–291

    Article  CAS  Google Scholar 

  35. Wagner E, McCaffery P, Mey J, Farhangfar F, Applebury ML, Dräger UC (1997) Retinoic acid increases arrestin mRNA levels in the mouse retina. FASEB J 11: 271–275

    PubMed  CAS  Google Scholar 

  36. McGinnis JF, Austin BJ, Stepanik PL, Lerious V (1994) Light-dependent regulation of the transcriptional activity of the mammalian gene for arrestin. J Neurosci Res 38: 479–482

    Article  PubMed  CAS  Google Scholar 

  37. Farber DB, Danciger JS, Organisciak DT (1991) Levels of mRNA encoding proteins of the cGMP cascade as a function of light environment. Exp Eye Res 53: 781–786

    Article  PubMed  CAS  Google Scholar 

  38. Weiler R, Schultz K, Pottek M, Tieding S, Janssen-Bienhold U (1998) Retinoic acid has light-adaptive effects on horizontal cells in the retina. Proc Nall Acad Sci USA 95: 7139–7144

    Article  CAS  Google Scholar 

  39. Mangelsdorf DJ, Thummel C, Beato M, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83: 835–839

    Article  PubMed  CAS  Google Scholar 

  40. Gudas LJ, Sporn MB, Roberts AB (1994) Cellular biology and biochemistry of the retinoids. In:MB Sporn, AB Roberts, DS Goodman (eds): The Retinoids: Biology Chemistry and Medicine. Raven Press, New York, 443–520

    Google Scholar 

  41. Tickle C Alberts B, Wolpert L, Lee J (1982) Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296: 564–566

    Article  PubMed  CAS  Google Scholar 

  42. Laudet V (1997) Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J Mol Endocrinol 19: 207–226

    Article  PubMed  CAS  Google Scholar 

  43. Picking WL, Chen D-M, Lee RD, Vogt ME, Polizzi JL, Marietta RG, Stark WS (1996) Control of Drosophila opsin gene expression by carotenoids and retinoic acid: Northern and Western analyses. Exp Eye Res 63: 493–500

    Article  PubMed  CAS  Google Scholar 

  44. Shim K, Picking WL, Kutty RK, Thomas CF, Wiggert BN, Stark WS (1997) Control of Drosophila retinoid and fatty acid binding glycoprotein expression by retinoids and retinoic acid: northern, western and immunocytochemical analyses. Exp Eye Res 65: 717–727

    Article  PubMed  CAS  Google Scholar 

  45. Saari JC (1994) Retinoids in photosensitive systems. In: MB Sporn, AB Roberts, DS Goodman (eds): The Retinoids: Biology Chemistry and Medicine. Raven Press, New York, 351–385

    Google Scholar 

  46. Dräger UC, Wagner E, McCaffery P (1998) Aldehyde dehydrogenases in the generation of retinoic acid in the developing vertebrate: a central role of the eye. J Nutr 128: 463S–466S

    PubMed  Google Scholar 

  47. Simon A, Hellman U, Wemstedt C, Eriksson U (1995) The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases. J Biol Chem 270: 1107–1112

    Article  PubMed  CAS  Google Scholar 

  48. Mertz JR, Shang E, Piantedosi R, Wei S, Wolgemuth DJ, Blaner WS (1997) Identification and characterization of a stereospecific human enzyme that catalyzes 9-cis-retinol oxidation. A possible role in 9-cis-retinoic acid formation. J Biol Chem 272: 11 744–11749

    Google Scholar 

  49. Driessen CA, Winkens HJ, Kuhlmann ED, Janssen AP, van Vugt AH, Deutman AF, Janssen JJ (1998) The visual cycle retinol dehydrogenase: possible involvement in the 9-cis retinoic acid biosynthetic pathway. FEBS Lett 428: 135–140

    Article  PubMed  CAS  Google Scholar 

  50. Desplan C (1997) Eye development: governed by a dictator or a junta? Cell 91: 861–864

    Article  PubMed  CAS  Google Scholar 

  51. Brodsky MH, Steller H (1996) Positional information along the dorsal-ventral axis of the Drosophila eye: graded expression of the four jointed gene. Dey Biol 173: 428–446

    Article  CAS  Google Scholar 

  52. Kastner P, Grondona JM, Mark M, Gansmuller A, LeMeur M, Decimo D, Vonesch J-L, Dollé P, Chambon P (1994) Genetic analysis of RXRa developmental function: convergence of RXR and RAR signalling pathways in heart and eye morphogenesis. Cell 78: 987–1003

    Article  PubMed  CAS  Google Scholar 

  53. Oro AE, McKeown M, Evans RM (1992) The Drosophila retinoid X receptor homolog ultraspiracle functions in both female reproduction and eye morphogenesis. Development, 115: 449–462

    PubMed  CAS  Google Scholar 

  54. Jones G, Sharp PA (1997) Ultraspiracle: an invertebrate nuclear receptor for juvenile hormones. Proc Nall Acad Sci USA 94: 13 499–13 503

    Google Scholar 

  55. Lammer EJ, Armstrong DL (1992) Malformations of hindbrain structures among humans exposed to isotretinoin (13-cis-retinoic acid) during early embryogenesis. In:GM Morris-Kay (ed.): Retinoids in normal development and teratogenesis. Oxford University Press, Oxford, 281–295

    Google Scholar 

  56. Mann I (1937) Developmental abnormalities of the eye. Cambridge University Press, Cambridge

    Google Scholar 

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Authors and Affiliations

  1. E. Kennedy Shriver Center and Department of Psychiatry, Harvard Medical School, 200 Trapelo Road, Waltham, MA, 02452, USA

    U. C. Dräger, E. Wagner & P. McCaffery

  2. E. Kennedy Shriver Center and Department of Neurology, Harvard Medical School, 200 Trapelo Road, Waltham, MA, 02452, USA

    A. Andreadis

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  1. U. C. Dräger
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  2. E. Wagner
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  3. P. McCaffery
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  4. A. Andreadis
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Editors and Affiliations

  1. Cattedra di Chimica Biologica, Istituto di Farmacologia e Farmacognosia, Università di Palermo, Via Forlanini 1, Palermo, I-90134, Italy

    Maria A. Livrea

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Dräger, U.C., Wagner, E., McCaffery, P., Andreadis, A. (2000). The role and evolutionary development of retinoic-acid signalling in the eye. In: Livrea, M.A. (eds) Vitamin A and Retinoids: An Update of Biological Aspects and Clinical Applications. MCBU Molecular and Cell Biology Updates. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8454-9_6

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  • DOI: https://doi.org/10.1007/978-3-0348-8454-9_6

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9574-3

  • Online ISBN: 978-3-0348-8454-9

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