Role of cell death in the topogenesis of neuronal distributions in the developing cat retinal ganglion cell layer
Authors: Wong R. O. L. , Hughes A. 
Published: January 2005

The neurons of the developing and adult ganglion cell layer of the cat retina may be morphologically divided into two major populations. One population, the classic neurons, is mainly composed of ganglion cells, and of a small percentage of displaced amacrines, the bar cells. The remaining neurons are microneurons, which make up the majority of the displaced amacrine population.

The loss of ganglion cells during the development has been attributed to cell death. It has alternatively been suggested that some ganglion cells may lose their axon and be transformed into displaced amacrine cells, without degeneration of the cell soma. Reexamination of foetal and postnatal cat retinas confirms the presence of degenerating cells in the ganglion cell layer. Their number appears to be at a maximum on embryonic day (E) 57 but declines rapidly until birth. The peak of cell death thus coincides with the decline in optic nerve fibre counts and classical neuron or ganglion cell numbers.

Some cells in early stages of degeneration resemble classical neurons, but the original morphology of those advanced stages of degeneration could not be identified, nor was it possible to identify pyknotic microneurons at any stage. Substantial degeneration of the microneurons is not suggested but if it occurs, it is masked by an overall increase in the population of these cells before birth. Cell death in the microneuron population thus cannot yet be ruled out.

It has been argued in the literature that fragments of degenerating cells in developing neural tissue are cleared by microglia within 10–14 hours. In order to test the hypothesis that operation of cell death can alone account for the observed loss of classical neurons in the foetal cat retina, we have modelled the effect of various presumed clearance times on corresponding neuronal population magnitudes. It is found that a constant clearance time of 10–24 hours would be consistent with the observed loss of classical neurons before birth. If this is true, then no ganglion cells would remain for transformation into amacrine cells.

The absolute density of degenerating or pyknotic cells is found to be relatively constant across the retina. However their density expressed as a percentage of the local population of classical neurons is markedly higher in peripheral than central retina. In the former region, they compose more than 10% of classical neurons at stage E57. On the same day, the percentage distribution maps define an elongated central area containing only 3–5% pyknotic profiles. This region corresponds to the location of the future visual streak. The low percentage of pyknotic cells relative to the classic neuron population may thus represent restricted cell death, leading to the corresponding high ganglion cell densities in the adult visual streak. The low percentage of pyknotic cells relative to the classic neuron population may thus represent restricted cell death, leading to the corresponding high ganglion cell densities in the adult visual streak. The process of differential cell death is thus revealed as having a potentially significant role in topogenesis.