Advertisement

Nitric Oxide in the Retina

Potential Involvement in Retinal Degeneration and Its Control by Growth Factors and Cytokines
  • O. Goureau
  • F. Becquet
  • Y. Courtois

Abstract

Nitric oxide (NO), an atmospheric gas, is now known to be enzymatically synthesized in a tightly regulated manner by a number of tissues and cell types. Over the past 5 years, significant progress has been made elucidating the mechanism of NO synthesis and the functions of NO in different biological systems. NO is produced by cells, and serves a wide variety of functions in different cells, ranging from vascular endothelia, immune cells, neurons and glia, hepatocytes and smooth muscle cells (reviewed in: 1–3). The functions of NO appear very diverse, having actions on vascular tone, neurotransmission (2), immune cytotoxicity (3,4), and many others. Three isoforms of NO synthase (NOS) have been identified as being responsible for this synthesis in the presence of oxygen, NADPH and flavins, and represent three distinct gene products (1). Two of the enzyme types are continuously present and, thus are termed constitutive NOS. The first, termed NOS-I is found in the cytosol of central and peripheral neurons (2), and the second (NOS-III) was originally expressed by the vascular endothelium. Small amounts of NO are generated by these two iso-enzymes when they are activated by the calcium/calmodulin complex. In contrast, NOS-II, or inducible NOS, is expressed in many cell types after challenge by immunological or inflammatory stimuli (3). This isoform, the activity of which is independent of calcium and calmodulin, generates large amounts of NO over longer periods which are dependent on the presence of the stimuli.

Keywords

Nitric Oxide Retinal Pigment Epithelial Cell Retinal Pigment Epithelial Photoreceptor Degeneration Retinal Pigment Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nathan, C.F., and Xie, Q. 1994. Nitric oxide synthases: Roles, tolls, and controls. Cell 78: 915–918.PubMedCrossRefGoogle Scholar
  2. 2.
    Bredt, D.S., and Snyder, S.H. 1994. Nitric oxide: a physiologic messenger molecule. Ann. Rev. Biochem. 63: 175–195.PubMedCrossRefGoogle Scholar
  3. 3.
    Nussler, A.K., and Billiar, T.R. 1993. Inflammation, immunoregulation, and inducible nitric oxide synthase. J. Leukoc. Biol. 54: 171–178.PubMedGoogle Scholar
  4. 4.
    Nathan, C.F., and Hibbs, J.B. Jr 1991. Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opinion Immunol 3: 65–70.CrossRefGoogle Scholar
  5. 5.
    Venturini, CM., Knowles, R.G., Palmer, R.M.J., and Moncada, S. 1991. Synthesis of nitric oxide in the bovine retina. Biochem. Biophys. Res. Comm. 180: 920–925.PubMedCrossRefGoogle Scholar
  6. 6.
    Goureau, O., Lepoivre, M., Mascarelli, F., and Courtois, Y. 1992. Nitric oxide synthase activity in bovine retina, In: Structures and functions of retinal proteins (Rigaud, J.L., and INSERM, eds) vol. 221, pp395–398. J. Libbey Eurotext Ltd, London.Google Scholar
  7. 7.
    Yamamoto, R., Bredt, D.S., Snyder, S.H., and Stone, R.A. 1993. The localization of nitric oxide synthase in the eye and related cranial ganglia. Neuroscience 54: 189–200.PubMedCrossRefGoogle Scholar
  8. 8.
    Osbome, N.N., Barnett, N.L., and Herrera, A.J. 1993. NADPH diaphorase localization and nitric oxide synthetase activity in the retina and anterior uvea of the rabbit eye. Brain Res. 610: 194–198.CrossRefGoogle Scholar
  9. 9.
    Koch, K., Lambrecht, H., Haberecht, M., Redburn, D., and Schimdt, H.H.H.W. 1994. Functional coupling of a calcium/calmodulin-dependent nitric oxide synthase and a soluble guanyl cyclase in vertebrate photoreceptor cells. EMBOJ. 13: 3312–3320.Google Scholar
  10. 10.
    Lieppe, B.A., Stone, C., Koistinaho, J., and Copenhagen, D.R. 1994. Nitric oxide synthase in Mü ller cells and neurons of salamander and fish retina. J. Neurosci. 14: 7641–7654.Google Scholar
  11. 11.
    Park, C., Pardhasaradhi, K., Gianotti, C., Villegas, E., and Krishna, G. 1994. Human retina expresses both constitutive and inducible isoforms of nitric oxide synthase mRNA. Biochem. Biophys. Res. Comm. 205: 85–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Miyachi, E.I., Murakami, M., and Nakaki, T. 1990. Arginine blocks gap junctions between retinal horizontal cells. Neuroreport 1: 107–110.PubMedCrossRefGoogle Scholar
  13. 13.
    Shiells, R., and Falk, G. 1992. Retinal on-bipolar cells contain a nitric oxide-sensitive guanylate cyclase. Neuroreport 3: 845–848.PubMedCrossRefGoogle Scholar
  14. 14.
    Ahmad, I., Leinders-Zufall, T., Kocsis, J.D., Shepherd, G.M., Zufall, F., and Barnstable, C.J. 1994. Retinal ganglion cells express a cGMP-gated cation conductance activatable by nitric oxide donors. Neuron 12: 155–165.PubMedCrossRefGoogle Scholar
  15. 15.
    Nö ll, G.N., Billek, M., Pietruck, C., and Schmidt, K.F. 1994. Inhibition of nitric oxide synthase alters light responses and dark voltage of amphibian photoreceptors. Neuropharmacology 33: 1407–1412.CrossRefGoogle Scholar
  16. 16.
    Kurenny, D.E., Moroz, L.L., Turner, R.W., Sharkey, K.A., and Barnes, S. 1994. Modulation of ion channels in rod photoreceptors by nitric oxide. Neuron 13: 315–324.PubMedCrossRefGoogle Scholar
  17. 17.
    Goureau O., Hicks, D., Courtois, Y., and de Kozak, Y. 1994. Induction and regulation of nitric oxide synthase in retinal Mü ller glial cells J. Neurochem. 63: 310–317.PubMedCrossRefGoogle Scholar
  18. 18.
    Goureau, O., Lepoivre, M., and Courtois, Y 1992. Lipopolysaccharide and cytokines induce a macrophage-type of nitric oxide synthase in bovine retinal pigmented epithelial cells. Biochem. Biophys. Res. Comm. 186: 854–859.PubMedCrossRefGoogle Scholar
  19. 19.
    Goureau, O., Hicks, D., and Courtois, Y. 1994 Human retinal pigmented epithelial cells produce nitric oxide in response to cytokines Biochem. Biophys. Res. Commun. 198: 120–126.PubMedCrossRefGoogle Scholar
  20. 20.
    Sparrow, J.R., Nathan, C.F., and Vodovotz, Y 1994. Cytokine regulation of nitric oxide oxide synthase in mouse retinal pigment epithelial cells in culture. Exp. Eye Res. 59: 129–139.PubMedCrossRefGoogle Scholar
  21. 21.
    Liversidge, J., Grabowski, P., Ralston, S., Benjamin, N., and Forrester, J.V. 1994. rat retinal pigment epithelial cells express an inducible form of nitric oxide synthase and produce NO in response to inflammatory cytokines and activated T cells. Immunolgy 83: 04–409.Google Scholar
  22. 22.
    Goureau, O., Lepoivre, M., Becquet, F., and Courtois, Y 1993. Differential regulation of inducible nitric oxide synthase by basic fibroblast growth factors and transforming growth factor ß in bovine retinal pigmented epithelial cells: Inverse correlation with cellular proliferation Proc Natl. Acad. Sci. USA 90: 4276–4280.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Goureau, O., and Courtois, Y 1994. Fibroblast growth factors inhibit inducible nitric oxide synthase expression in bovine retinal pigmented epithelial cells. In: The Biology of Nitric Oxide, (Moncada, S., Feelisch, M., Busse, R., and Higgs, E.A., eds) Vol.4, pp105–108, Portland Press Ltd, London.Google Scholar
  24. 24.
    Becquet, F., Courtois, Y, and Goureau, O. 1994. Nitric oxide decreases in vitro phagocytosis of photoreceptor outer segments by bovine retinal pigmented epithelial cells. J. Cell. Physiol. 159: 256–262.PubMedCrossRefGoogle Scholar
  25. 25.
    Digheiro, P., Reux, I., Hauw, JJ., Fillet, AM., Courtois, Y and Goureau, O. 1994. Expression of inducible nitric oxide synthase in cytomegalovirus-infected glial cells of retinas from AIDS patients. Neurosci. Letters, 166: 31–34.Google Scholar
  26. 26.
    Bellot, J., Goureau, O., Thillaye, B., Chatenoud, L., and de Kozak, Y 1994. Inhibition of endotoxin-induced uveitis by nitric oxide synthase inhibitor; effect on intraocular TNF and NO synthesis”.In: Advances in Ocular Immunology, (Nussenblatt, R.B., Whitcup, S.M., Caspi, R., and Gery, I., eds) pp225–228, Elsevier Science B.V., New York.Google Scholar
  27. 27.
    Mandai M., Yoshimura, N., Yoshida, M., Iwaki, M. and Honda Y 1994. The role of nitric oxide synthase in endotoxin-induced uveitis: effect of NG-nitro L-arginine. Invest. Ophthalmol. Vis. Sci. 35: 3673–3681.PubMedGoogle Scholar
  28. 28.
    Organisciak, D.T., Darrow, R.M., Bicknell, I.R., Jiang, Y.L., Pickford, M., and Blanks, J. 1991. Protection against retinal light damage by natural and synthetic antioxidants. In: Retinal Degenerations. (Anderson, R.E., Hollyfield, J.G., and LaVail, M.M., eds) pp 189–201, Boca Raton, CRC Press.Google Scholar
  29. 29.
    Davidson, P.C., and Sterneberg, P. Jr. 1993. Potential retinal phototoxicity. Am. J. Ophthalmol. 116: 497–501.PubMedCrossRefGoogle Scholar
  30. 30.
    Goureau, O., Jeanny, JC, Becquet, F., Harthmann, MR, and Courtois, Y. 1994. Protection against light-induced retinal degeneration by an inhibitor of NO synthase inhibitor. Neuroreport 5: 233–236.CrossRefGoogle Scholar
  31. 31.
    Ehret-Hilberer, S., Nullans, G., Aunis, D., and Virmaux, N. 1992. Mono ADP-ribosylation of transducin catalyzed by rod outer segment extract. FEBS Lett. 309: 394–398.PubMedCrossRefGoogle Scholar
  32. 32.
    Zoche, M., and Koch, K.W. 1995. Purified retinal nitric oxide synthase enhances ADP-ribosylation of rod outer segments proteins. FEBS Lett. 357: 178–182.PubMedCrossRefGoogle Scholar
  33. 33.
    Beckman, J.S., and Crow, J.P. 1993. Pathological implications of nitric oxide, Superoxide and peroxynitrite formation. Biochem. Soc. Trans. 21: 330–334.PubMedGoogle Scholar
  34. 34.
    Stamler, J.S. 1994. Redox Signaling: Nitrosylation and related target interactions of Nitric Oxide. Cell 78: 931–936.PubMedCrossRefGoogle Scholar
  35. 35.
    Malecaze, F., Mathis, A., Arne, J.L., Raulais, D., Courtois, Y., and Hicks D. 1991. Localization of acidic fibroblast growth factor in proliferative vitreoretinopathy membranes. Current Eye Res. 10, 719–729.CrossRefGoogle Scholar
  36. 36.
    Dawson D.A. 1994. Nitric Oxide and focal ischemia: multiplicity of actions and diverse outcome Cerebrovasc. Brain Metab.Rev. 6: 299–324.Google Scholar
  37. 37.
    Faktorovitch, E.G., Steinberg, R.G., Yasumura, D., and LaVail, M. 1990. Photoreceptor degeneration in inherited retinal distrophy delayed by basic fibroblast growth factor. Nature 347: 83–86.CrossRefGoogle Scholar
  38. 38.
    Faktorovitch, E.G., Steinberg, R.G., Yasumura, D., Matthes, M.T., and LaVail, M. 1992. Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat. J. Neurosc. 12, 3554–3567.Google Scholar
  39. 39.
    La Vail, M., Unoki, K., Yasumara, D., Matthes, M.T., Yancopoulos G.D., and Steinberg R.G. 1992. Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc. Natl. Acad. Sci. USA 89, 11249–11253.CrossRefGoogle Scholar
  40. 40.
    Unoki K., LaVail M. 1994. Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor and basic fibroblast growth factor. Invest. Ophtalmol. Vis. Sci. 35, 907–915.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • O. Goureau
    • 1
  • F. Becquet
    • 1
  • Y. Courtois
    • 1
  1. 1.Unité de Recherches GérontologiquesInstitut National de la Santé et de la Recherche Médicale Association Claude BernardParisFrance

Personalised recommendations