Chronic Administration of Phenyl N-TERT- Butylnitrone Protects the Retina Against Light Damage

  • Isabelle Ranchon
  • Jeremy White
  • Sherry Chen
  • Kathleen Alvarez
  • Yashige Kotake
  • Robert E. Anderson


Retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. Most are the results of mutations expressed in either photoreceptor or retinal pigment epithelial cells. There is currently no treatment by which the primary disorder can be modified, although researchers around the world are working on different potential therapeutic approaches to treat retinal degenerations. These are based on the possibility of transfecting the photoreceptor or retinal epithelial cells with a functioning gene, transplanting photoreceptor or retinal pigment epithelial cells into the sub-retinal space, using electronic devices to stimulate the retina, or administrating drugs to enhance the repair/defense systems of the retina. Although encouraging success has been shown in animals models, gene therapy1, transplantation2 or injection of growth factors3,4,5 require invasive intraocular procedures and some have significant side effects.


Optic Nerve Retinal Pigment Epithelial Cell Retinal Degeneration Outer Nuclear Layer Osmotic Pump 
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  1. 1.
    M. Cayouette, D. Behn, M. Sedtner, P. Lachapelle, C. Gravel, Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse, J. Neurosci. 18,9282–9293 (1998).PubMedGoogle Scholar
  2. 2.
    F. Ghosh, B. Ehinger, Full-thickness retinal transplants: a review. Ophthalmologica 214,54–69 (2000)PubMedCrossRefGoogle Scholar
  3. 3.
    M.M. LaVail, D. Yasumura, M.T. Matthes, C Lau-Villacorta, K Unoki, CH Sung, RH Steinberg, Protection of mouse photoreceptors by survival factors in retinal degenerations, Invest. Ophthalmol Vis Sci. 39, 592–602 (1998)PubMedGoogle Scholar
  4. 4.
    E.G. Faktorovich, R.H. Steinberg, D. Yasumura, M.T. Matthes, M.M. LaVail Photoreceptor degeneration in inherited retinal dystrophy delayed by fibroblast growth factor, Nature 347,83–86 (1990)PubMedCrossRefGoogle Scholar
  5. 5.
    M.M LaVail, K. Unok, D. Yasumura, M.T. Matthes, G.D. Yancopoulos, R.E. Steinberg, Multiple growth factors, cytokines and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc. Natl. Acad. Sci. USA 89,11249–11253 (1992)PubMedCrossRefGoogle Scholar
  6. 6.
    E.L. Berson, B. Rosner, M.A. Sandberg, K.C. Hayes, B.W. Nicholson, C. Weigel-DiFranco, W.A. Willett, Randomized trial of Vitamin A and E supplementation for retinitis pigmentosa. Arch. Ophthalmol. 111,761–772 (1993).PubMedCrossRefGoogle Scholar
  7. 7.
    R.W. Massof, D. Finkelstein, Supplemental Vitamin A retards loss of ERG amplitude in retinitis pigmentosa. Arch. Ophthalmol. 111,751–754 ( 1993)PubMedCrossRefGoogle Scholar
  8. 8.
    D.T. Organisciak, R.M. Darrow, I.R. Bicknell, Y.L. Jiang, M. Pickford, J.C. Blanks,Protection against retinal light damage by natural and synthetic antioxidants. In: Retinal Degenerations, edited by R.E. Anderson, J.G. Hollyfield, M.M. LaVail (Plenum Press, New York and London, 1991), pp. 189–201.Google Scholar
  9. 9.
    D.T. Organisciak, R.M. Darrow, Y-L. Jiang, G.E. Marak, J.C. Blanks, Protection by dimethylthiourea against retinal light damage in rats. Invest. Ophthalmol. Vis. Sci. 33,1599–1609(1992)PubMedGoogle Scholar
  10. 10.
    I. Ranchon, J.M. Gorrand, J. Cluzel, M-T. Droy-Lefaix, M. Doly Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Invest. Ophthalmol. Vis. Sci. 40,1191–1199 (1999).PubMedGoogle Scholar
  11. 11.
    I. Ranchon, J. White, S. Chen, K. Alvarez, R.E. Anderson, Systemic Administration of Phenyl-N-tert-butylnitrone Protects the Retina from Light Damage. Submitted to Invest. Ophthalmol. Vis. Sci. (2000)Google Scholar
  12. 12.
    J.L. Poyer, R.A. Floyd, P.B. McCay, K.G. Janszen, E.R. David. Spin trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane. Biochim. Biophys. Acta, 539,402–409 (1978).PubMedCrossRefGoogle Scholar
  13. 13.
    J.L. Poyer, P.B. McCay, E.K. La, K.G. Janzen, E.R. David, Confirmation of assignment of the trichloromethyl radical spin adduct detected by spin trapping during 13C-carbon tetrachloride metabolism in vitro and in vivo. Biochem. Biophys. Res. Commun. 94,1154–1160 (1980).PubMedCrossRefGoogle Scholar
  14. 14.
    B.S. Winkler, M.E. Boulton, J.D. Gottsch, P. Sternberg, Oxidative damage and age related macualr degeneration, Molecular Vision, 5,32 (1999).PubMedGoogle Scholar
  15. 15.
    I. Ranchon, J.M. Gorrand, J. Cluzel, J.C. Vennat, M. Doly. Light-induced variations of retinal sensitivity in rats. Curr. Eye Res. 17, 14–23 (1998).PubMedCrossRefGoogle Scholar
  16. 16.
    L.M. Rapp, M.I. Naasn, R.D. Wiegand, et al. Morphological and biochemical comparison between retinal regions having differing susceptibility to photoreceptor degeneration. In: Retinal Degeneration: Experimental and Clinical Studies, edited by M.M. La Vail, J.G. Hollyfield, R.E. Anderson (New York: Alan RLiss, 1985) pp. 421–437.Google Scholar
  17. 17.
    W.K. Noell, V.S. Waker, B.S. Kang, S. Berman. Retinal damage by light in rats.Invest. Ophthalmol, 5(5), 450–473 (1966).PubMedGoogle Scholar
  18. 18.
    R.D. Wiegand, N.M. Giusto, L.M. Rapp, R.E. Anderson. Evidence for rod outer segment lipid peroxidation following constant light illumination of the rat retina. Invest. Ophthalmol. Vis Sci., 24,1433–1435 (1983).PubMedGoogle Scholar
  19. 19.
    D.T. Organisciak, H.M. Wang, Z.Y. Li, M.O.M. Tso, The protective effect of ascorbate in retinal light damage of rats. Invest. Ophthalmol. Vis. Sci. 26,1580–1588 (1985).PubMedGoogle Scholar
  20. 20.
    L. Feeney, E.R. Berman, Oxygen toxicity: membrane damage by free radicals. Invest. Ophthalmol. Vis. Sci. 15, 789–792 (1976).Google Scholar
  21. 21.
    D.T. Organisciak, I.R. Bicknell, R.M. Darrow, The effect of L and D ascorbic acid administration on retinal tissue levels and light damage in rats. Curr. Eye. Res. 11,231–241 (1992).PubMedCrossRefGoogle Scholar
  22. 22.
    W.T. Ham, H.A. Muller, J.J. Ruffolo, J.J.E. Millen, S.F. Cleary, R.K. Guerry, D Guerry, Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr. Eye. Res. 3,165–174 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    J. Li, D.P. Edward, T.T. Lam, M.O.M. Tso, Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea. Exp. Eye Res. 56,71–78 (1993).PubMedCrossRefGoogle Scholar
  24. 24.
    Y. Kotake, H. Sang, T. Miyajima, G.L. Wallis, Inhibition of NF-kappaB, iNOS mRNA, COX2 mRNA, and COX catalytic activity by phenyl-N-tert-butylnitrone (PBN). Biochim. Biophys. Acta, 1448:77–84 (1998).PubMedCrossRefGoogle Scholar
  25. 25.
    T. Tabatabaie, K.L. Graham, A.M. Vasquez, R.A. Floyd, Y. Kotake, Inhibition of the cytokine-mediated inducible nitric oxide synthase expression in rat insulinoma cells by phenyl N-terf-butylnitrone. Nitric Oxide 4,157–67 (2000).PubMedCrossRefGoogle Scholar
  26. 26.
    H. Pogrebniak, M. Merino, S. Hahn, J. Mitchell, H. Pass, Spin trap salvage from endotoxemia: the role of cytokine down-regulation, Surgery 112,130–139 (1992).PubMedGoogle Scholar
  27. 27.
    H. Sang, G.L. Wallis, C.A. Stewar, Y. Kotake, Expression of cytokines and activation of transcription factors in lipopolysaccharide-administered rats and their inhibition by phenyl N-tert-butylnitrone (PBN). Arch. Biochem. Biophys. 363:341–348 (1999).PubMedCrossRefGoogle Scholar
  28. 28.
    C.A. Stewart, K. Hyam, G. Wallis, et al. Phenyl-N-terf-butylnitrone demonstrates broad-spectrum inhibition of apoptosis-associated gene expression in endotoxin-treated rats. Arch. Biochem. Biophys. 363,:71–74 (1999).CrossRefGoogle Scholar
  29. 29.
    M. Tsuji, O. Inanami, M. Kuwabara. Neuroprotective effect of alpha-phenyl-N-terf-butylnitrone in gerbil hippocampus is mediated by the mitogen-activated protein kinase pathway and heat shock proteins. Neurosci. Lett. 282,41–44 (2000).PubMedCrossRefGoogle Scholar
  30. 30.
    K.A. Robinson, C.A. Stewart, Q. Pye, R.A. Floyd, K. Hensley. Basal phosphorylation is decreased and phosphatase activity increased by an antioxidant and a free radical trap in Primary rat glia. Arch. Biochem. Biophys. 365,211–215 (1999).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Isabelle Ranchon
    • 1
    • 3
  • Jeremy White
    • 1
  • Sherry Chen
    • 1
    • 3
  • Kathleen Alvarez
    • 1
    • 3
  • Yashige Kotake
    • 4
  • Robert E. Anderson
    • 1
    • 2
    • 3
  1. 1.Department of OphthalmologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Cell BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  3. 3.Dean A. McGee Eye InstituteOklahoma CityUSA
  4. 4.Oklahoma Medical Research FoundationOklahoma CityUSA

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