The time-course and extent of death of retinal ganglion cells (RGCs) following ablation of the superior colliculus (SC) in neonatal Wistar rats has recently been described [Harvey, A. R. and Robertson, D. (1992) J. Comp. Neurol., 325, 83-94]. Normal and pyknotic nuclei of retinotectally projecting ganglion cells were visualized using the fluorescent retrograde tracer diamidino yellow (DY), which had been injected into the SC at P2 (day of birth = PO), 2 days prior to tectal removal. The present report sets out to determine whether cycloheximide, an inhibitor of protein synthesis, or ganglioside GM1 reduced this lesion-induced RGC death. All surgery was carried out under ether anaesthesia; DY was injected into the left SC at P2 and the injected area was removed at P4. Cycloheximide (20-500 ng) was injected into the vitreous chamber of the right eye immediately after the lesion and again 11-12 h later. In some rats, cycloheximide administration was delayed until 12 h after the SC ablation, Control rats received SC lesions alone or lesions plus sham eye injections of saline. Different doses of GM1 were applied i.p. or intraocularly. Rats were perfused 24 h after the SC lesion, at the time of peak RGC death. Retinae of lesion only or sham eye injected rats contained similar to 11% pyknotic RGCs and the density of normal RGCs was similar to 3400/mm(2). The rate of pyknosis in cycloheximide treated retinae was reduced to similar to 3%. Normal RGC density in these retinae was similar to 5500/mm(2), similar to that found in retinae of unlesioned animals. Delaying the application of cycloheximide significantly reduced its effectiveness in preventing RGC death. GM1 treatments had no, or only minor, impact on RGC pyknosis 24 h after SC removal. The data are consistent with the proposal that RGC death after neonatal loss of central target sites is an active process that requires protein synthesis. It is therefore possible that, in the developing mammalian visual system, target-derived neurotrophic factors maintain RGC viability by suppressing some form of endogenous suicide program within the neurons.
|Journal||European Journal of Neuroscience|
|Publication status||Published - 1994|
Harvey, A., Cui, Q., & Robertson, D. (1994). The effect of cycloheximide and ganglioside GM1 on the viability of retinotectally projecting ganglion cells following ablation of the superior colliculus in neonatal rats. European Journal of Neuroscience, 6, 550-557. https://doi.org/10.1111/j.1460-9568.1994.tb00299.x