Nitric Oxide in the Retina
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.
KeywordsNitric Oxide Retinal Pigment Epithelial Cell Retinal Pigment Epithelial Photoreceptor Degeneration Retinal Pigment Epithelial Cell
Unable to display preview. Download preview PDF.
- 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
- 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.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
- 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.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.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
- 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.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
- 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
- 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
- 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
- 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