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α-Crystallin Protected Axons from Optic Nerve Degeneration After Crushing in Rats

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Abstract

In mature mammals, optic nerve injury results in apoptosis of retinal ganglion cells. The literature confirms that lens injury enhances retinal ganglion cells survival, but the mechanism is not very clear. Using silver staining method and computer image analysis techniques, the effect of α-crystallin, a major component of the lens in the survival of retinal ganglion cell axons, was investigated in vivo after intravitreal injections. The results showed that enhanced survival of axotomized axons was observed beyond the crush site after a single intravitreal administration of α-crystallin at the time of axotomy. Axonal density of the retinal ganglion cell was significantly greater than in the untreated controls until 2 weeks after injection. This effect declined by 4 weeks after injection but survival of axons remained greater than controls. These findings indicate that α-crystallin plays a key role in protecting axons after optic nerve injury.

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References

  • Alge, C. S., Priglinger, S. G., Neubauer, A. S., et al. (2002). Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin. Investigative Ophthalmology and Visual Science, 43, 3575–3582.

    PubMed  Google Scholar 

  • Andley, U. P. (2007). Crystallins in the eye: Function and pathology. Progress in Retinal and Eye Research, 26, 78–98.

    Article  PubMed  CAS  Google Scholar 

  • Andley, U. P., Song, Z., Wawrousek, E. F., & Bassnett, S. (1998). The molecular chaperone alphaA-crystallin enhances lens epithelial cell growth and resistance to UVA stress. Journal of Biological Chemistry, 273, 31252–31261.

    Article  PubMed  CAS  Google Scholar 

  • Bai, F., Xi, J., Higashikubo, R., & Andley, U. P. (2004). Cell kinetic status of mouse lens epithelial cells lacking alphaA- and alphaB-crystallin. Molecular and Cellular Biochemistry, 265, 115–122.

    Article  PubMed  CAS  Google Scholar 

  • Berkelaar, M., Clarke, D. B., Wang, Y. C., Bray, G. M., & Aguayo, A. J. (1994). Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. Journal of Neuroscience, 14, 4368–4374.

    PubMed  CAS  Google Scholar 

  • Bhat, S. P., Horwitz, J., Srinivasan, A., & Ding, L. (1991). Alpha B-crystallin exists as an independent protein in the heart and in the lens. European Journal of Biochemistry, 202, 775–781.

    Article  PubMed  CAS  Google Scholar 

  • Carmignoto, G., Maffei, L., Candeo, P., Canella, R., & Comelli, C. (1989). Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. Journal of Neuroscience, 9, 1263–1272.

    PubMed  CAS  Google Scholar 

  • Cavusoglu, N., Thierse, D., Mohand-Said, S., et al. (2003). Differential proteomic analysis of the mouse retina: The induction of crystallin proteins by retinal degeneration in the rd1 mouse. Molecular & Cellular Proteomics, 2, 494–505.

    CAS  Google Scholar 

  • Clark, J. I., & Muchowski, P. J. (2000). Small heat-shock proteins and their potential role in human disease. Current Opinion in Structural Biology, 10, 52–59.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, A., Bray, G. M., & Aguayo, A. J. (1994). Neurotrophin-4/5 (NT-4/5) increases adult rat retinal ganglion cell survival and neurite outgrowth in vitro. Journal of Neurobiology, 25, 953–959.

    Article  PubMed  CAS  Google Scholar 

  • Cui, Q., & Harvey, A. R. (2000). CNTF promotes the regrowth of retinal ganglion cell axons into murine peripheral nerve grafts. Neuroreport, 11, 3999–4002.

    Article  PubMed  CAS  Google Scholar 

  • Derham, B. K., & Harding, J. J. (1999). Alpha-crystallin as a molecular chaperone. Progress in Retinal and Eye Research, 18, 463–509.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, D., Heiduschka, P., & Thanos, S. (2001). Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Experimental Neurology, 172, 257–272.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, D., Pavlidis, M., & Thanos, S. (2000). Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Investigative Ophthalmology and Visual Science, 41, 3943–3954.

    PubMed  CAS  Google Scholar 

  • Ge, J., Li, Y., Zhuo, Y., & Guo, Y. (1998). Peripheral nerve and transgene cells transplantation in the treatment of experimental neuropathy of SD rats. Yan Ke Xue Bao., 14, 121–125.

    PubMed  CAS  Google Scholar 

  • Ghosh, J. G., Estrada, M. R., & Clark, J. I. (2005). Interactive domains for chaperone activity in the small heat shock protein, human alphaB crystallin. Biochemistry, 44, 14854–14869.

    Article  PubMed  CAS  Google Scholar 

  • Ghosh, J. G., Shenoy, A. K., & Clark, J. I. (2006). N- and C-Terminal motifs in human alphaB crystallin play an important role in the recognition, selection, and solubilization of substrates. Biochemistry, 45, 13847–13854.

    Article  PubMed  CAS  Google Scholar 

  • Hadani, M., Harel, A., Solomon, A., Belkin, M., Lavie, V., & Schwartz, M. (1984). Substances originating from the optic nerve of neonatal rabbit induce regeneration-associated response in the injured optic nerve of adult rabbit. Proceedings of the National Academy of Sciences of the United States of America, 81, 7965–7969.

    Article  PubMed  CAS  Google Scholar 

  • Heiduschka, P., Fischer, D., & Thanos, S. (2005). Recovery of visual evoked potentials after regeneration of cut retinal ganglion cell axons within the ascending visual pathway in adult rats. Restorative Neurology and Neuroscience, 23, 303–312.

    PubMed  Google Scholar 

  • Horwitz, J. (1992). Alpha-crystallin can function as a molecular chaperone. Proceedings of the National Academy of Sciences of the United States of America, 89, 10449–10453.

    Article  PubMed  CAS  Google Scholar 

  • Jones, S. E., Jomary, C., Grist, J., Thomas, M. R., & Neal, M. J. (1998). Expression of alphaB-crystallin in a mouse model of inherited retinal degeneration. Neuroreport, 9, 4161–4165.

    Article  PubMed  CAS  Google Scholar 

  • Kamradt, M. C., Chen, F., & Cryns, V. L. (2001). The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. Journal of Biological Chemistry, 276, 16059–16063.

    Article  PubMed  CAS  Google Scholar 

  • Leon, S., Yin, Y., Nguyen, J., Irwin, N., & Benowitz, L. I. (2000). Lens injury stimulates axon regeneration in the mature rat optic nerve. Journal of Neuroscience, 20, 4615–4626.

    PubMed  CAS  Google Scholar 

  • Liu, X., Hawkes, E., Ishimaru, T., Tran, T., & Sretavan, D. W. (2006). EphB3: an endogenous mediator of adult axonal plasticity and regrowth after CNS injury. Journal of Neuroscience, 26, 3087–3101.

    Article  PubMed  CAS  Google Scholar 

  • Lorber, B., Berry, M., & Logan, A. (2005). Lens injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage- and lens-derived factors. European Journal of Neuroscience, 21, 2029–2034.

    Article  PubMed  Google Scholar 

  • Mansour-Robaey, S., Clarke, D. B., Wang, Y. C., Bray, G. M., & Aguayo, A. J. (1994). Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proceedings of the National Academy of Sciences of the United States of America, 91, 1632–1636.

    Article  PubMed  CAS  Google Scholar 

  • Masilamoni, J. G., Jesudason, E. P., Baben, B., Jebaraj, C. E., Dhandayuthapani, S., & Jayakumar, R. (2006). Molecular chaperone alpha-crystallin prevents detrimental effects of neuroinflammation. Biochimica Et Biophysica Acta, 1762, 284–293.

    PubMed  CAS  Google Scholar 

  • Mehlen, P., Kretz-Remy, C., Préville, X., & Arrigo, A. P. (1996). Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. EMBO Journal, 15, 2695–2706.

    PubMed  CAS  Google Scholar 

  • Mey, J., & Thanos, S. (1993). Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo. Brain Research, 602, 304–317.

    Article  PubMed  CAS  Google Scholar 

  • Ohto-Fujita, E., Fujita, Y., & Atomi, Y. (2007). Analysis of the alphaB-crystallin domain responsible for inhibiting tubulin aggregation. Cell Stress and Chaperones, 12, 163–171.

    Article  PubMed  CAS  Google Scholar 

  • Organisciak, D., Darrow, R., Gu, X., Barsalou, L., & Crabb, J. W. (2006). Genetic, age and light mediated effects on crystallin protein expression in the retina. Photochem Photobiol, 82, 1088–1096.

    Article  PubMed  CAS  Google Scholar 

  • Parcellier, A., Schmitt, E., Brunet, M., Hammann, A., Solary, E., & Garrido, C. (2005). Small heat shock proteins HSP27 and alphaB-crystallin: Cytoprotective and oncogenic functions. Antioxidants & Redox Signalling, 7, 404–413.

    Article  CAS  Google Scholar 

  • Rabacchi, S. A., Ensini, M., Bonfanti, L., Gravina, A., & Maffei, L. (1994). Nerve growth factor reduces apoptosis of axotomized retinal ganglion cells in the neonatal rat. Neuroscience, 63, 969–973.

    Article  PubMed  CAS  Google Scholar 

  • Regini, J. W., Grossmann, J. G., Burgio, M. R., et al. (2004). Structural changes in alpha-crystallin and whole eye lens during heating, observed by low-angle X-ray diffraction. Journal of Molecular Biology, 336, 1185–1194.

    Article  PubMed  CAS  Google Scholar 

  • Rogalla, T., Ehrnsperger, M., Preville, X., et al. (1999). Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. Journal of Biological Chemistry, 274, 18947–18956.

    Article  PubMed  CAS  Google Scholar 

  • Sawai, H., Clarke, D. B., Kittlerova, P., Bray, G. M., & Aguayo, A. J. (1996). Brain-derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganglion cells. Journal of Neuroscience, 16, 3887–3894.

    PubMed  CAS  Google Scholar 

  • Schwartz, M., Belkin, M., & Harel, A. (1985). Regenerating fish optic nerves and a regeneration-like response in injured optic nerves of adult rabbits. Science, 228, 600–603.

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan, A. N., Nagineni, C. N., & Bhat, S. P. (1992). alpha A-crystallin is expressed in non-ocular tissues. Journal of Biological Chemistry, 267, 23337–23341.

    PubMed  CAS  Google Scholar 

  • Stege, G. J., Renkawek, K., Overkamp, P. S., et al. (1999). The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. Biochemical and Biophysical Research Communications, 262, 152–156.

    Article  PubMed  CAS  Google Scholar 

  • Stupp, T., Pavlidis, M., Busse, H., & Thanos, S. (2005). Lens epithelium supports axonal regeneration of retinal ganglion cells in a coculture model in vitro. Experimental Eye Research, 81, 530–538.

    Article  PubMed  CAS  Google Scholar 

  • Sun, Y., & MacRae, T. H. (2005). The small heat shock proteins and their role in human disease. FEBS Journal, 272, 2613–2627.

    Article  PubMed  CAS  Google Scholar 

  • Wong, W. K., Cheung, A. W., & Cho, E. Y. (2006). Lens epithelial cells promote regrowth of retinal ganglion cells in culture and in vivo. Neuroreport, 17, 699–704.

    Article  PubMed  Google Scholar 

  • Xi, J. H., Bai, F., & Andley, U. P. (2003). Reduced survival of lens epithelial cells in the alphaA-crystallin-knockout mouse. Journal of Cell Science, 116, 1073–1085.

    Article  PubMed  CAS  Google Scholar 

  • Yin, Y., Cui, Q., Li, Y., et al. (2003). Macrophage-derived factors stimulate optic nerve regeneration. Journal of Neuroscience, 23, 2284–2293.

    PubMed  CAS  Google Scholar 

  • Yin, Y., Henzl, M. T., Lorber, B., et al. (2006). Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nature Neuroscience, 9, 715–717.

    Article  CAS  Google Scholar 

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Correspondence to Yi Wang or David T. Yew.

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Ying, X., Zhang, J., Wang, Y. et al. α-Crystallin Protected Axons from Optic Nerve Degeneration After Crushing in Rats. J Mol Neurosci 35, 253–258 (2008). https://doi.org/10.1007/s12031-007-9010-1

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  • DOI: https://doi.org/10.1007/s12031-007-9010-1

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