Blockade of Proteolytic Activity Retards Retrograde Degeneration of Axotomized Retinal Ganglion Cells and Enhances Axonal Regeneration in Organ Cultures

  • Solon Thanos
Chapter
Part of the NATO ASI Series book series (NSSA, volume 222)

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.

Keywords

Optic Nerve Ganglion Cell Microglial Cell Retinal Ganglion Cell Ganglion Cell Layer 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Solon Thanos
    • 1
  1. 1.Res. Laboratory, Dept. of OphthalmologyUniversity of Tübingen, School of MedicineTübingenGermany

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