¡¡¡¡RESULTS

¡¡¡¡After 21 days of chronic ocular hypertension the retina became thinner (28.3¡À8.0, 17.0¡À6.5¦Ìm, P<0.05) and the number of RGC decreased as compared with control group. In the control group only trace amount of Nogoª²A was detected in the layer of ganglion cells in the retina. In the retina from rat model with chronic ocular hypertension, the level of Nogoª²A protein(IOD) were found to increase at 7 days (64.17¡À2.68, 24.93¡À1.31¦Ìm, P<0.01) after establishment of the model, and the increase remained significantly at 28 days (37.69¡À3.15, 24.93¡À1.31¦Ìm, P<0.05) after the model establishment compared with control group(Figure 1).

¡¡¡¡DISCUSSION

¡¡¡¡Optic nerve damage of glaucoma is a chronic course. However, most animal models for glaucoma research are ischemiaª²reperfusion models and have disadvantage for observation of retina protection. Reports about morphological changes under chronic ocular hypertension are rare. Regenerative nerve fiber growth and structural plasticity are limited in the CNS of adult mammalian, including optic nerve, in part because of the presence of neurite growth inhibitory constituents[2]. An important step in elucidating the mechanisms of this inhibition was the discovery of Nogoª²A, which is an oligodendrocyteª²associated neurite growth inhibitor[3ª²5]. The nogo gene encodes three major protein products, Nogoª²A, ª²B, and ª²C, by alternative splicing and alternative promoter usage[6,7]. Nogoª²A was shown to be inhibitory for fibroblast spreading and neurite outgrowth and to induce growth cone collapse in rat dorsal root ganglion (DRG) and chick retinal ganglion cell (RGC) neurons. Our results suggest the change of expression of Nogoª²A protein in the retina was associated with the elevated ocular pressure. The dramatically increased Nogoª²A indicated that Nogoª²A may play an important role in obstructing regeneration of optic nerve. Suppression of the Nogoª²A might be a new treatment for glaucoma.

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¡¡¡¡1 Belien ATJ, Paganetti PA, Schwab ME. Membraneª²type 1 matrix metalloprotease (MT1ª²MMP) enables invasive migration of glioma cells in central nervous system white matter. J Cell Biol 1999;144:373ª²383

¡¡¡¡2 Behar O, Mizuno K, Neumann S, Woolf CJ. Putting the spinal cord together again. Neuron 2000;26:291ª²293

¡¡¡¡3 Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME. Nogoª²A is a myelinª²associated neurite outgrowth inhibitor and an antigen for monoclonal antibody INª²1. Nature 2000;403:434ª²439

¡¡¡¡4 GrandPr¨¦ T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 2000;403:439ª²444

¡¡¡¡5 Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michalovich D, Simmons DL, Walsh FS. Inhibitor of neurite outgrowth in humans. Nature 2000;403:383ª²384

¡¡¡¡6 Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME. Nogoª²A is a myelinª²associated neurite outgrowth inhibitor and an antigen for monoclonal antibody INª²1. Nature 2000;403:434ª²439

¡¡¡¡7 Oertle T, Huber C, van der Putten H, Schwab ME. Genomic structure and functional characterisation of the promoters of human and mouse Nogo/Rtnª²4. J Mol Biol 2003;325:299ª²323

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