Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats

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Journal of Neuroscience, Vol 14, 4368-4374, Copyright © 1994 by Society for Neuroscience

ARTICLE

Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats

M Berkelaar, DB Clarke, YC Wang, GM Bray and AJ Aguayo
Centre for Research in Neuroscience, Montreal General Hospital Research Institute, Quebec, Canada.
Using quantitative anatomical techniques, we show that after intraorbital optic nerve transection in adult rats, virtually all retinal ganglion cells (RGCs) survive for 5 d and then die abruptly in large numbers, reducing the RGC population to approximately 50% of normal by day 7 and to less than 10% on day 14. During this period of rapid cell loss, some RGCs show cytochemical alterations indicative of apoptosis ("programmed cell death"), a change not previously categorized after axotomy in adult mammals. With intracranial lesions 8- 9 mm from the eye, the onset of cell death is delayed until day 8 and is greater with cut than crush. The demonstration that axotomy results in apoptosis, the long interval between axonal injury and RGC death, and the different time of onset of the massive RGC loss with optic nerve lesions near or far from the eye suggest that axonal interruption triggers a cascade of molecular events whose outcome may be critically dependent on the availability of neuronal trophic support from endogenous or exogenous sources. The role of such molecules in RGC survival and the reversible nature of these injury-induced changes is underscored by the temporary rescue of most RGCs by a single intravitreal injection of brain-derived neurotrophic factor during the first 5 d after intraorbital optic nerve injury (Mansour-Robaey et al., 1994). The delayed pattern of RGC loss observed in the present experiments likely explains such a critical period for effective neurotrophin administration.

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M. Fagiolini, M. Caleo, E. Strettoi, and L. Maffei
Axonal Transport Blockade in the Neonatal Rat Optic Nerve Induces Limited Retinal Ganglion Cell Death
J. Neurosci., September 15, 1997; 17(18): 7045 - 7052.
[Abstract] [Full Text] [PDF]

L. A. Kerrigan, D. J. Zack, H. A. Quigley, S. D. Smith, and M. E. Pease
TUNEL-Positive Ganglion Cells in Human Primary Open-angle Glaucoma
Arch Ophthalmol, August 1, 1997; 115(8): 1031 - 1035.
[Abstract] [PDF]

M. Alexiades and C. Cepko
Subsets of retinal progenitors display temporally regulated and distinct biases in the fates of their progeny
Development, January 3, 1997; 124(6): 1119 - 1131.
[Abstract] [PDF]

V. Porciatti, T. Pizzorusso, M.�C. Cenni, and L. Maffei
The visual response of retinal ganglion cells is not altered by optic nerve transection in transgenic mice�overexpressing�Bcl-2
PNAS, December 10, 1996; 93(25): 14955 - 14959.
[Abstract] [Full Text] [PDF]

L. Bonfanti, E. Strettoi, S. Chierzi, M. C. Cenni, X.-H. Liu, J.-C. Martinou, L. Maffei, and S. A. Rabacchi
Protection of Retinal Ganglion Cells from Natural and Axotomy-Induced Cell Death in Neonatal Transgenic Mice Overexpressing bcl-2
J. Neurosci., July 1, 1996; 16(13): 4186 - 4194.
[Abstract] [Full Text] [PDF]

H. Sawai, D. B. Clarke, P. Kittlerova, G. M. Bray, and A. J. Aguayo
Brain-Derived Neurotrophic Factor and Neurotrophin-4/5 Stimulate Growth of Axonal Branches from Regenerating Retinal Ganglion Cells
J. Neurosci., June 15, 1996; 16(12): 3887 - 3894.
[Abstract] [Full Text] [PDF]

L. A. Levin and A. Louhab
Apoptosis of Retinal Ganglion Cells in Anterior Ischemic Optic Neuropathy
Arch Ophthalmol, April 1, 1996; 114(4): 488 - 491.
[Abstract] [PDF]

S. Schumacher, M. Jung, U. Norenberg, A. Dorner, R. Chiquet-Ehrismann, C. A. O. Stuermer, and F. G. Rathjen
CALEB Binds via Its Acidic Stretch to the Fibrinogen-like Domain of Tenascin-C or Tenascin-R and Its Expression Is Dynamically Regulated after Optic Nerve Lesion
J. Biol. Chem., March 2, 2001; 276(10): 7337 - 7345.
[Abstract] [Full Text] [PDF]