Advertisement

Molecular and Cellular Biochemistry

, Volume 301, Issue 1–2, pp 155–163 | Cite as

Degenerative and apoptotic events at retinal and optic nerve level after experimental induction of ocular hypertension

  • Nicola Calandrella
  • Gianfranco Scarsella
  • Nicola Pescosolido
  • Gianfranco Risuleo
Original Paper

Abstract

Ocular hypertension is a symptom of a glaucomatous condition characterized by a severe vision decrease. Blindness caused by the apoptotic death of the retinal ganglion cells and of the astrocytes of the optic nerve may eventually result. Experimental hypertension was induced by inoculation of methylcellulose in the anterior chamber. Chromatin staining, TUNEL assay, and inter-nucleosomal DNA fragmentation observed in retina and optic nerve strongly suggest that hypertension causes apoptosis. Immunolocalization of the fibrillary acidic glial protein, specific of cell stress, and caspase-3 in the same tissues, further support this mode of cell death. Activation of the ubiquitin dependant proteolytic system was also observed. Protection from apoptosis exerted by administration of the peroxide scavenger trolox, suggests that the apoptotic pathway is activated by an oxidative stress. The data presented here show that the experimental hypertensive insult induces degenerative and apoptotic events comparable to those observed in human glaucoma.

Keywords

Experimental hypertension Glaucoma Retina Optic nerve Apoptosis 

Notes

Acknowledgements

This work was partially supported by Italian Ministry for Education (MIUR, Grants to GR and GS) and the EUROMED laboratories – Guidonia, Italy (Grant to GR). The very pertinent and useful observations of an anonymous reviewer allowed a substantial improvement of the manuscript and are, therefore, also acknowledged.

References

  1. 1.
    Quigley HA (1987) Reappraisal of the mechanism of glaucomatous optic nerve damage. Eye 1:318–322PubMedGoogle Scholar
  2. 2.
    De Gregorio F, Pecori-Giraldi J, De Stefano C, Virno M (1997) Correlation between ocular hypertension induced by ibopamine and perimetric defect in primary open angle glaucoma. Eur J Ophthalmol 7:152–155PubMedGoogle Scholar
  3. 3.
    Friedman DS, Wilson MR, Liebmann JM, Fechtner RD, Weinreb RN (2004) An evidence based assessment of risk factors for the progression of ocular hypertension and glaucoma. Am J Ophthalmol Rev 138:19–31CrossRefGoogle Scholar
  4. 4.
    Quigley HA, Enger C, Katz J, Sommer A, Scott R, Gilbert D (1994) Risk factors for the development of glaucomatous visual field loss in ocular hypertension. Arch Ophthalmol 112:644–649PubMedGoogle Scholar
  5. 5.
    Quigley HA, McKinnon SJ, Zack DJ, Pease ME, Kerrigan-Baumrind LA, Kerrigan FD, Mitchell RS (2000) Retrograde axonal trasport of BDNF in retinal ganglion cell is blocked by acute IOP elevation in rat. Invest Ophthalmol Vis Sci 41:3460–3466PubMedGoogle Scholar
  6. 6.
    Sommers A, Tielsh JM, Katz J (1991) Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. Arch Ophthalmol 109:1090–1095Google Scholar
  7. 7.
    Wax MB, Tezel G, Kobayashi S, Hernandez MR (2000) Responses of different cells lines from ocular tissues to elevated hydrostatic pressure. Br J Ophthalmol 84:423–428PubMedCrossRefGoogle Scholar
  8. 8.
    Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes-implications for their role in neurologic disease. Neuroscience 54:15–36PubMedCrossRefGoogle Scholar
  9. 9.
    Barnett NL, Pow DV, Bull ND (2001) Differential perturbation of neuronal and glial glutamate transport system in retinal ischemia. Neurochem Int 39:291–299PubMedCrossRefGoogle Scholar
  10. 10.
    McKinnon SJ (1997) Glaucoma, apoptosis and neuroprotection. Curr Opin Ophthalmol 8:28–37PubMedCrossRefGoogle Scholar
  11. 11.
    Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:374–386Google Scholar
  12. 12.
    Noremberg MD (1994) Astrocyte responses to CNS injury. J Neuropatol Exp Neurol 3:213–220CrossRefGoogle Scholar
  13. 13.
    Hernandez MR, Pena JD (1997) The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol 115:389–395PubMedGoogle Scholar
  14. 14.
    Ye H, Hernandez MR (1995) Heterogeneity of astrocytes in human optic nerve head. J Comp Neurol 4:441–452CrossRefGoogle Scholar
  15. 15.
    Ricard CS, Kobayashi S, Pena JDO, Salvador-Silva M, Agapova O, Hernandez MR (2000) Selective expression of neuronal cell adhesion molecule (NCAM)-180 in optic nerve head astrocytes exposed to elevated hydrostatic pressure in vitro. Mol Brain Res 81:62–79PubMedCrossRefGoogle Scholar
  16. 16.
    Varela HJ, Hernandez MR (1997) Astrocyte responses in human optic nerve head with primary open angle glaucoma. Journal of glaucoma 6:303–313PubMedCrossRefGoogle Scholar
  17. 17.
    Lieth E, Barber AJ, Xu B (1998) Glial reactivity and impaired glutamate metabolism in short term experimantal diabetic retinopathy. Diabetes 47:815–820PubMedCrossRefGoogle Scholar
  18. 18.
    Mizutani M, Gerhardinger C, Lorenzi M (1998) Müller cell changes in human diabetic retinophahaty. Diabetes 47:445–449PubMedCrossRefGoogle Scholar
  19. 19.
    Erickson PA, Fisher SK, Guerin CJ, Anderson DH, Kaska DD (1987) Glial fibrillary acidic protein increases in Müller cells after retinal detachment. Exp Eye Res 44:37–48PubMedCrossRefGoogle Scholar
  20. 20.
    Guidry C, Medeiros NE, Curcio CA (2002) Phenotypic variation of retinal pigment epithelium in age-related macular degeneration. Invest Ophthalmol Vis Sci 43:266–273Google Scholar
  21. 21.
    Tanihara H, Hangai M, Sawaguchi S, Abe H, Kageyama M, Nakazawa F, Shirasawa E, Honda Y (1997) Up-regulation of glial fibrillary acidic protein in the retina of primate eyes with experimental glaucoma. Arch Ophthalmol 115:752–756PubMedGoogle Scholar
  22. 22.
    Wang X, Tay SSW, Ng YK (2000) An immunohistochemical study of neuronal and glial cell reaction in retina of rats with experimental glaucoma. Exp Brain Res 132:476–484PubMedCrossRefGoogle Scholar
  23. 23.
    Wang L, Cioffi A, Dong J, Fortune B (2002) Immunohistologic evidence for retinal glial cell changes in human glaucoma. Invest Ophthalmol Vis Sci 43:1088–1094PubMedGoogle Scholar
  24. 24.
    Yuan L, Neufeld AH (2000) Tumor necrosis factor-alpha: a potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head. Glia 32:42–50PubMedCrossRefGoogle Scholar
  25. 25.
    Bonfoco E, Kranic D, Ankarcrona M, Nicotera P, Lipton SA (1995) Apoptosis and necrosis: two distinct event induced respective by mild and intense insult with NMDA or nitric oxide/superosside in cortical cell cultures. Proc Natl Acad Sci 92:7162–7166PubMedCrossRefGoogle Scholar
  26. 26.
    Cotinet A, Goureau O, Hicks D (1997) Tumor necrosis factor and nitric oxide production by Retinal Müller glial cell from rats exhibiting inherited retinal dystrophy. Glia 1:59–69CrossRefGoogle Scholar
  27. 27.
    Dugan LL, Sensi SL, Canzoniero LM (1995) Mithocondrial production of reactive oxygen species in cortical neurons after exposure to N-methyl-D-aspartate. J Neurosci 10:6377–6388Google Scholar
  28. 28.
    Neufeld AH (1999) Nitric oxide: a potential mediator of retinal ganglion cell damage in glaucoma. Surv Ophthalmol 43:129–135CrossRefGoogle Scholar
  29. 29.
    Raivich G, Bohatschek M, Kloss CUA, Werner A, Jones LL, Kreutzberg WG. (1999) Neuroglial activation repertoire in the injured brain: graded response, molecular mechanism and cues to physiological function. Brain Res Rev 30:77–105PubMedCrossRefGoogle Scholar
  30. 30.
    Tezel G, Wax MB (2000) Increased production of tumor necrosis factor by glial cells exposed to simulate ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J Neurosci 23:8693–8700Google Scholar
  31. 31.
    Salvador-Silva M, Ricard CS, Agapova OA, Yang P, Hernandez MR (2001) Expression of small heat shock protein and intermediate filaments in the human optic nerve head astrocytes exposed to elevated hydrostatic pressure in vitro. J Neurosci Res 66:59–73PubMedCrossRefGoogle Scholar
  32. 32.
    Hernandez MR (2000) The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res 3:297–321CrossRefGoogle Scholar
  33. 33.
    Tezel G, Hernandez MR, Wax MB (2001) In vitro evaluation of reactive astrocyte migration, a component of tissue component remodeling in glaucomatous optic nerve head. Glia 3:178–189CrossRefGoogle Scholar
  34. 34.
    Yang Y, Fang S, Jensen JP, Weissman AM, Ashwell JD (2000) Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288:874–877PubMedCrossRefGoogle Scholar
  35. 35.
    Bresin A, Iacoangeli A, Risuleo G, Scarsella G (2001) Ubiquitin depend proteolysis is activated in apoptotic fibroblasts in culture. Mol Cell Biochem 220:57–60PubMedCrossRefGoogle Scholar
  36. 36.
    Naash MI, Al-Ubaidi MR, Andreson RE (1997) Light exposure induces ubiquitin conjugation and degradation activities in the rat retina. Invest Ophthalmol Vis Sci 38:2344–2354PubMedGoogle Scholar
  37. 37.
    Lee JC, Peter ME (2003) Regulation of apoptosis by ubiquitination. Immunol Rev 193:39–47PubMedCrossRefGoogle Scholar
  38. 38.
    Risuleo G, Cristofanilli M, Scarsella G (2003) Acute ischemia/hypoxia in rat hippocampal neurons activates nuclear ubiquitinand alters both chromatin and DNA. Mol Cell Biochem 250:73–80PubMedCrossRefGoogle Scholar
  39. 39.
    Ben-Shlomo G, Bakalash S, Lambrou GN, Latour E, Dawson WW, Schwartz M, Ofri R (2005) Pattern electroretinography in a rat model of ocular hypertension: functional evidence for early detection of inner retinal damage. Exp Eye Res 81:340–349PubMedGoogle Scholar
  40. 40.
    Kanamori A, Nakamura M, Nakanishi Y, Yamada Y, Negi A (2005) Long-term glial reactivity in rat retinas ipsilateral and contralateral to experimental glaucoma. Exp Eye Res 81:48–56PubMedCrossRefGoogle Scholar
  41. 41.
    Moreno MC, Aldana Marcos HJ, Croxatto O, Sande PH, Campanelli J, Jaliffa CO, Benozzi J, Rosenstein RE (2005) A new experimental model of glaucoma in rats through intracameral injections of hyaluronic acid. Exp Eye Res 81:71–80PubMedCrossRefGoogle Scholar
  42. 42.
    McClain DE, Kalinich JF, Ramakrishnan N (1995) Trolox inhibits apoptosis in irradiated MOLT-4 lymphocytes. FASEB J 9:1345–1354PubMedGoogle Scholar
  43. 43.
    Zhu MD, Cai FY (1992) Development of experimental chronic intraocular hypertension in the rabbit. Austl Nw Z J Ophthalmol 20:225–234Google Scholar
  44. 44.
    Drize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity ofsubstances applied topically to the skin and mucous membranes. J Pharm Exp Ther 82:377–390Google Scholar
  45. 45.
    Savada A, Neufeld AH (1999) Confirmation of the model of chronic, moderately elevated intraocular pressure. Exp Eye Res 69:525–531CrossRefGoogle Scholar
  46. 46.
    Jesenberger V, Jentsch S (2002) Deadly encounter: ubiquitin meets apoptosis. Nat Rev Mol Cell Biol. 3:112–121PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Nicola Calandrella
    • 1
  • Gianfranco Scarsella
    • 1
  • Nicola Pescosolido
    • 2
  • Gianfranco Risuleo
    • 3
  1. 1.Dipartimento di Biologia Cellulare e dello SviluppoUniversità di Roma “La Sapienza”RomeItaly
  2. 2.Dipartimento di Scienze dell’ invecchiamento Sezione di OftalmologiaUniversità di Roma “La Sapienza”RomeItaly
  3. 3.Dipartimento di Genetica e Biologia MolecolareUniversità di Roma “La Sapienza”RomeItaly

Personalised recommendations