Degenerative and apoptotic events at retinal and optic nerve level after experimental induction of ocular hypertension
- 131 Downloads
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.
KeywordsExperimental hypertension Glaucoma Retina Optic nerve Apoptosis
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.
- 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
- 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
- 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
- 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
- 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
- 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.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