Advertisement

The Hypoxic Transcriptome of the Retina: Identification of Factors with Potential Neuroprotective Activity

  • Markus Thiersch
  • Wolfgang Raffelsberger
  • Enrico Frigg
  • Marijana Samardzija
  • Patricia Blank
  • Olivier Poch
  • Christian Grimm
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

Most blinding diseases of the retina share a common feature – the loss of photoreceptor cells by apoptosis. Although degenerative diseases like age–related macular degeneration (AMD) and Retinitis Pigmentosa (RP) are among the main causes for severe visual impairment and blindness, no effective therapeutical treatments are available to prevent loss of vision in human patients. Protection of retinal cells against cell death is a promising strategy to develop therapies aiming at the rescue of retinal function. For the successful design of neuroprotective strategies, it is essential to understand the molecular events leading to the degeneration of retinal cells. To study signaling pathways and molecular mechanisms during the degenerative processes, several mouse models of inherited retinal degeneration are used (Fauser et al., 2002).

Keywords

Photoreceptor Cell Intermittent Hypoxia Retinal Degeneration Hypoxic Precondition Normoxic Control 
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. Aviram, M., Rosenblat, M., Bisgaier, C.L., Newton, R.S., Primo-Parmo, S.L., and La Du, B.N. 1998. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 101(8): 1581–1590.PubMedCrossRefGoogle Scholar
  2. Benjamini, Y. and Hochberg, Y. 1995. Controlling the false discovery rate – a practical and powerful approach to multiple testing. J Roy Stat Soc 57: 289–300.Google Scholar
  3. Bocker-Meffert, S., Rosenstiel, P., Rohl, C., Warneke, N., Held-Feindt, J., Sievers, J., and Lucius, R. 2002. Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats. Invest Ophthalmol Vis Sci 43(6): 2021–2026.PubMedGoogle Scholar
  4. Buck, M. and Chojkier, M. 2003. Signal transduction in the liver: C/EBPbeta modulates cell proliferation and survival. Hepatology 37(4): 731–738.PubMedCrossRefGoogle Scholar
  5. Cai, Z., Manalo, D.J., Wei, G., Rodriguez, E.R., Fox-Talbot, K., Lu, H., Zweier, J.L., and Semenza, G.L. 2003. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation 108(1): 79–85.PubMedCrossRefGoogle Scholar
  6. Dong, J.W., Zhu, H.F., Zhu, W.Z., Ding, H.L., Ma, T.M., and Zhou, Z.N. 2003. Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression. Cell Res 13(5): 385–391.PubMedCrossRefGoogle Scholar
  7. Draghici, S., Khatri, P., Bhavsar, P., Shah, A., Krawetz, S.A., and Tainsky, M.A. 2003a. Onto-Tools, the toolkit of the modern biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Nucleic Acids Res 31(13): 3775–3781.Google Scholar
  8. Draghici, S., Khatri, P., Martins, R.P., Ostermeier, G.C., and Krawetz, S.A. 2003b. Global functional profiling of gene expression. Genomics 81(2): 98–104.Google Scholar
  9. Draghici, S., Khatri, P., Shah, A., and Tainsky, M.A. 2003c. Assessing the functional bias of commercial microarrays using the onto-compare database. Biotechniques Suppl: 55–61.Google Scholar
  10. Emerson, M.R., Nelson, S.R., Samson, F.E., and Pazdernik, T.L. 1999. A global hypoxia preconditioning model: neuroprotection against seizure-induced specific gravity changes (edema) and brain damage in rats. Brain Res Brain Res Protoc 4(3): 360–366.PubMedCrossRefGoogle Scholar
  11. Fauser, S., Luberichs, J., and Schuttauf, F. 2002. Genetic animal models for retinal degeneration. Surv Ophthalmol 47(4): 357–367.PubMedCrossRefGoogle Scholar
  12. Gidday, J.M., Fitzgibbons, J.C., Shah, A.R., and Park, T.S. 1994. Neuroprotection from ischemic brain injury by hypoxic preconditioning in the neonatal rat. Neurosci Lett 168(1–2): 221–224.PubMedCrossRefGoogle Scholar
  13. Grimm, C., Wenzel, A., Groszer, M., Mayser, H., Seeliger, M., Samardzija, M., Bauer, C., Gassmann, M., and Reme, C.E. 2002. HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med 8(7): 718–724.PubMedCrossRefGoogle Scholar
  14. Grimm, C., Wenzel, A., Stanescu, D., Samardzija, M., Hotop, S., Groszer, M., Naash, M., Gassmann, M., and Reme, C. 2004. Constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration. J Neurosci 24(25): 5651–5658.PubMedCrossRefGoogle Scholar
  15. Ke, Q. and Costa, M. 2006. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 70(5): 1469–1480.PubMedCrossRefGoogle Scholar
  16. Koury, M.J., Sawyer, S.T., and Brandt, S.J. 2002. New insights into erythropoiesis. Curr Opin Hematol 9(2): 93–100.PubMedCrossRefGoogle Scholar
  17. Mahyar-Roemer, M. and Roemer, K. 2001. p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. Oncogene 20(26): 3387–3398.PubMedCrossRefGoogle Scholar
  18. Maxwell, P. 2003. HIF-1: an oxygen response system with special relevance to the kidney. J Am Soc Nephrol 14(11): 2712–2722.PubMedCrossRefGoogle Scholar
  19. Miyashita, K., Itoh, H., Arai, H., Suganami, T., Sawada, N., Fukunaga, Y., Sone, M., Yamahara, K., Yurugi-Kobayashi, T., Park, K., Oyamada, N., Sawada, N., Taura, D., Tsujimoto, H., Chao, T.H., Tamura, N., Mukoyama, M., and Nakao, K. 2006. The neuroprotective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential. Endocrinology 147(4): 1642–1653.PubMedCrossRefGoogle Scholar
  20. Naumann, U., Weit, S., Wischhusen, J., and Weller, M. 2001. Diva/Boo is a negative regulator of cell death in human glioma cells. FEBS Lett 505(1): 23–26.PubMedCrossRefGoogle Scholar
  21. Samardzija, M., Wenzel, A., Naash, M., Reme, C.E., and Grimm, C. 2006. Rpe65 as a modifier gene for inherited retinal degeneration. Eur J Neurosci 23(4): 1028–1034.PubMedCrossRefGoogle Scholar
  22. Sharp, F.R. and Bernaudin, M. 2004. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 5(6): 437–448.PubMedCrossRefGoogle Scholar
  23. Song, Q., Kuang, Y., Dixit, V.M., and Vincenz, C. 1999. Boo, a novel negative regulator of cell death, interacts with Apaf-1. Embo J 18(1): 167–178.PubMedCrossRefGoogle Scholar
  24. Wenzel, A., Grimm, C., Samardzija, M., and Reme, C.E. 2005. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24(2): 275–306.PubMedCrossRefGoogle Scholar
  25. Wenzel, A., Reme, C.E., Williams, T.P., Hafezi, F., and Grimm, C. 2001. Mat The Rpe65 Leu450Met variation increases retinal resistance against light-induced degeneration by slowing rhodopsin regeneration. J Neurosci 21(1): 53–58.PubMedGoogle Scholar
  26. Yu, D.Y. and Cringle, S.J. 2005. Retinal degeneration and local oxygen metabolism. Exp Eye Res 80(6): 745–751.PubMedCrossRefGoogle Scholar
  27. Zaman, K., Ryu, H., Hall, D., O’Donovan, K., Lin, K.I., Miller, M.P., Marquis, J.C., Baraban, J.M., Semenza, G.L., and Ratan, R.R. 1999. Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-1/CREB and increased expression of glycolytic enzymes, p21(waf1/cip1), and erythropoietin. J Neurosci 19(22): 9821–9830.PubMedGoogle Scholar
  28. Zhang, S.X. and Ma, J.X. 2007. Ocular neovascularization: Implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 26(1): 1–37.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Markus Thiersch
    • 1
  • Wolfgang Raffelsberger
    • 2
  • Enrico Frigg
    • 3
  • Marijana Samardzija
    • 3
  • Patricia Blank
    • 3
  • Olivier Poch
    • 4
  • Christian Grimm
    • 5
  1. 1.Lab for Retinal Cell Biology, Dept Ophthalmology, CIHPUniversity of ZurichSwitzerland
  2. 2.Laboratoire de BioInformatique et Génomique Intégrative (IGBMC)StrasbourgFrance
  3. 3.Lab for Retinal Cell Biology, Dept Ophthalmology, CIHPUniversity of ZurichSwitzerland
  4. 4.Laboratoire de BioInformatique et Génomique Intégrative (IGBMC)StrasbourgFrance
  5. 5.Lab for Retinal Cell Biology, Dept Ophthalmology, CIHP, Lab for Retinal Cell BiologyUniversity of Zurich, University Eye HospitalZurichSwitzerland

Personalised recommendations