Retinal ganglion cell survival and neurite regeneration requirements: the change from Müller cell dependence to superior colliculi dependence during development

Abstract

A study has been made of the effects of Müller conditioned media or neonatal superior collicular extracts on the survival in dissociate culture of retinal ganglion cells (RGC) from differently aged rats. Embryonic and neonatal RGC were identified either by retrograde horseradish peroxidase (HRP) or Thy-1 antibody labelling techniques. Müller conditioned media supported the survival, over 24 h in culture, of 85% of the RGC plated from 17-day embryos (E17); in contrast, superior collicular extract only maintained 45% of these RGC. With further development there was a decline in the survival enhancing effects of the Müller conditioned media and an increase in the survival due to superior collicular extracts: by postnatal day 12 (P12), the survival of RGC had declined to 20% in the Müller media, but had increased to over 90% in the colliculus extract. This transition in the dependence of RGC from Müller cells to superior colliculi was examined with homogeneous cultures of RGC, obtained using cell sorting techniques. RGC in these cultures showed the same transition in dependence from Müller cells to superior colliculi, indicating that the survival-enhancing effects were not mediated by the other intrinsic cells of the retina. The results suggest that the survival of RGC is at first dependent on the intrinsic glia of the retina and only later, as development proceeds, on the targets of the RGC in the superior colliculus. The normal RGC death period in the rat extends from near birth to about 6 days postnatal 32,34. The question then arises as to the timing of trophic support from Müller glia and from neurones in the tectum in relation to the duration of the normal RGC death period. This has been examined in the present work.