Abstract
Observations concerning the consequences of injury to the central nervous system, to the spinal cord and to the retina of higher vertebrates can be traced back to the early decades of the century (Cajal, 1928; James, 1933; Eayrs, 1952). In accord with these observations, which have been confirmed later, the course of retrograde adult retinal ganglion cell degeneration commences a few days after intraorbital transection of the optic nerve and progresses during the weeks and months following the axotomy, finally resulting in depletion of the retinal ganglion cell layer (GCL) (Richardson et al. 1982; Barron et al. 1986; Thanos, 1988; Villegas-Perez et al. 1988; Carmignoto et al. 1989). The failure of lesioned ganglion cells to regrow their axons within the distal portion of the optic nerve is assumed to be caused by the presence of differentiated oligodendrocytes whose myelin exerts inhibiting influences both on embryonic (Schwab and Caroni, 1988) and on adult ganglion cell axons (Vanselow et al. 1990). In addition to the inhibiting environment, insufficient growth-supporting agents within the optic nerve (Cajal, 1928) have been assumed to determine the fate of lesioned neurons, namely the progressive degeneration. External neurotrophic influences introduced by the apposition of peripheral nerve segments at the time of severing the optic nerve could rescue some ganglion cells, which then can regenerate into growth-permitting peripheral nerve transplants (Vidal-Sanz et al. 1987; Villegas-Perez et al. 1988). Factors released from peripheral nerves also support regrowth of axons in cultured retinal explants (Thanos et al. 1989). The responsiveness of lesioned ganglion cells to external administration of nerve growth factor (NGF) during the first weeks after lesion (Carmignoto et al., 1989) is in line with all previous observations that epigenetic influences can regulate the quantities of neurons which survive axotomy.
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References
Barde, Y.A., D. Edgar, and H. Thoenen,1982, Purification of a new neurotrophic factor from mammalian brain. EMBO-J. 1:549–553.
Barron, K.D., M. P. Dentinger, G. Lrohel, S.K. Easton, and R. Mankes, 1986, Qualitative and ultrastructaral observations on retinal ganglion cell layer of rat after intraorbital nerve crush. J. Neurocvtol. 15: 345–362.
Bignami, A., and D. Dahl, 1979, The radial glia of Müller and their response to injury. An Immunofluorescence study with antibodies to the glial fibrillary acidic (GFA) protein. Exp. Eve Res. 28: 63–69.
Cajal, R. y. S., 1928, Degeneration and regeneration of the nervous system. (R.M. May. Trans.) University Press, London and New York.
Cammermeyer, J.,1970, The life history of the microglia cell: A light microscopic study. In: S. Ehrenpreis and O. C. Solnitzky (eds): Neurosciences Research, Vol. 3, Academic Press, New York, pp. 44–129.
Carmignoto, G., L. Maffei, P. Candeo, R. Canella and C. Comelli, 1989, Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. J. Neurosci. 9: 1263–1272.
del Rio-Hortega, P., 1932, Microglia. In: Cytology and Cellular Pathology of the nervous system (eds. Penfield W.), pp. 482–534. Paul B. Hoeber, New York.
Grafstein, B., and N.A. Ingoglia, 1982, Intracranial transection of the optic nerve in adult mice: Preliminary observations. Exp. Neurol. 76: 318–330.
Giulian, D., 1987, Ameboid microglia as effectors of inlamation in the central nervous system. J. Neurosci. Res. 18:155–171.
Giulian, D., J. Chen, J. E. Ingeman, J. K. George, and M. Noponen, 1989, The role of mononuclear phagocytes in wound-healing after traumatic injury to adult mammalian brain. J.Neurosci. 9(12): 4416–4429.
Giulian, D., 1990, Microglia and tissue damage in the central nervous system. In: Differentation and functioning of Glial cells, Ed. Levi, Alan R. Liss, pp. 379–389.
Hickey, W.F., and H. Kimura, 1988, Perivascular microglial cells of the CNS are bone-derived and present antigen in vivo. Science, 239:290–292.
Gebhard, W., H. Tschesche, and H. Fritz, 1986, Biochemistry of aprotinin and aprotinin-like inhibitors. In: proteinase inhibitors (A. J. Barrett and J. Salvesen, eds), Elsevier, pp. 375–378.
James, G. R., 1933, Degeneration of ganglion cell following axonal injury. Arch. Ophthalmol. 9: 338–343.
Keirstead, S.A., M. Rasminsky, Y. Fukuda, D.A. Carter, A.J. Aguayo and M. Vidal-Sanz, 1989, Electrophysiological responses in hamster superior colliculus evoked by regenerating retinal axons. Science, 246: 255–257.
Lampson, L.A., 1987, Molecular basis of the immune response to neural antigens. TINS 10: 211–216.
Lieberman, A. R., 1971, The axon reaction: A review of the principal features of perikaryal responses to axon injury. Int. Rev. Neurobiol. 14: 49–124.
Murabe, Y., and Y. Sano, 1981, Thiaminepyrophosphatase activity in the plasma membrane of microglia. Histochem. 71: 45–52.
Perry, V. H., 1979, The ganglion cell layer in the retina of the rat. Proc. R. Soc. Lond. B204: 363–375.
Perry, V. H., and S. Gordon, 1988, Macrophages and microglia in the nervous system. TINS, Vol. 11, No. 6, 273–277.
Politis, M.J., and P. S. Spencer, 1986, Regeneration of rat optic axons into peripheral nerve grafts. Exp. Neurol. 91: 52–59.
Powers, C. J. and J. W. Harper, 1986, Inhibitors of serine proteases. In: Proteinase inhibitors (A. J. Barrett and G. S. Salvesen, eds) Elsevier, pp. 55–152.
Rich, D. H., 1986, Inhibitors of cysteine proteinases. In: proteinase inhibitors (A. J. Barrett and G. salvesen, eds.) Elsevier, pp. 179–217.
Schnebli, H. P., 1975, The effects of protease inhibitors on cells in vitro. In: Proteases and Biological Control. (Eds. E. Reich, D. B. Rifkin and E. Shaw), Cold Spring Harbor Conferences on cell proliferation. pp. 785–794.
Schnitzer J. and J. Scherer, 1990, Microglial cell responses in the rabbit retina following transection of the optic nerve. J. Comp. Neurol. 302: 779–791.
Schwab, M.E. and P. Caroni, 1988, Oligodendrocytes and CNS myelin are non-permissive for neurite growth and fibroblast spreading in vitro. J. Neurosci.8: 2381–2393.
Sievers, J., Hausmann, B., Unsicker, K., and M. Berry, 1987, Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve. Neurosci. Lett. 76: 157–162.
Singer, P.A., S. Mehler, and H. L. Fernandez, 1982, Blockade of retrograde axonal transport delays the onset of metabolic and morphologic changes induced by axotomy. J. Neurosci. 2: 1299–1306.
Stoll, G., B.D. Trapp, and J.W. Griffin, 1989, Macrophage function during Wallerian degeneration of the rat optic nerve: Clearance of degenerating myelin and Ia expression. J. Neurosci. 9: 2327–2335.
Streit, W.J., M.B. Graeber and G.W. Kreutzberg, 1990, Functional plasticity of microglia: a review GLIA, 1(5) 301–307.
Tello, F., 1907, La regeneration de voies optigues. Trab. Lab. Invest. Biol. 5: 237–248.
Thanos, S., 1988, Alterations in the morphology of ganglion cell dendrites in the adult rat retina after optic nerve transection and grafting of peripheral nerve segements. Cell Tiss. Res. 259: 599–609.
Thanos, S., M. Bähr, Y. A. Barde, and J. Vanselow, 1989, Survival and axonal elongation of adult rat retinal ganglion cells. In vitro effects of lesioned sciatic nerve and brain derived-neurotrophic factor. E. J. Neurosci. 1: 19–26.
Thanos, S. and J. Vanselow, 1990, Fetal tectal transplants in the cortex of adult rats become innervated both by retinal ganglion cell axons regenerating through peripheral nerve grafts and by cortical neurons. Rest. Neurol. Neurosci. 2: 63–75.
Vanselow, J., M. E. Schwab and S. Thanos, 1990, Responses of regenerating rat retinal ganglion cell axons to contacts with central nervous myelin in vitro. E.J. Neurosci. 2: 121–125.
Vidal-Sanz, M., G. M. Bray, M. P. Villegas-Perez, S. Thanos and A. J. Aguayo, 1987, Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J. Neurosci. 7: 2894–2909.
Villegas-Perez, M. P., Vidal-Sanz, M., G. M. Bray and Albert Aguayo, 1988, Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. J. Neurosci. 8(1): 265–280.
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Thanos, S. (1991). Blockade of Proteolytic Activity Retards Retrograde Degeneration of Axotomized Retinal Ganglion Cells and Enhances Axonal Regeneration in Organ Cultures. In: Bagnoli, P., Hodos, W. (eds) The Changing Visual System. NATO ASI Series, vol 222. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3390-0_7
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