Müller (glial) cells in the teleost retina: consequences of continuous growth.

In the continuously enlarging eye of teleost fishes retinal growth is achieved by the generation of new cells and by stretching the existing tissue. As a consequence of stretching, the density for most neurons decreases except for rod photoreceptors, which are produced by stem cells in the outer nuclear layer (ONL). We investigated retinal Müller glial cells with immunocytochemical markers against vimentin and glutamine synthetase in animals of various sizes. In addition, we used Western immunoblot analysis to investigate the changes in the glia-specific enzyme glutamine synthetase in the enlarging retina. We found that in the cichlid fish Haplochromis burtoni the density of Müller cells decreases from about 14 cells/mm2 to 4 cells/mm2 with increasing body size. Since it is known that the density of rod photoreceptors remains constant, it follows that the neuron to Müller cell ratio increases in the growing eye. In our estimates, this ratio ranges from around 54:1 in small fish to more than 67:1 in larger animals. Quantified Western blots revealed that the amount of glutamine synthetase per retinal area does not change in the growing eye, which means that the amount of this enzyme in each Müller cell must increase. Staining isolated cells and retinal sections from small and large fish with an antibody against glutamine synthetase showed stronger immunoreactivity in larger animals, especially in the areas of the photoreceptor cell bodies and outer limiting membrane and a more extensive branching of Müller cell processes. Thus, Müller cells in growing fish appear to compensate for the increasing metabolic challenge and are able to maintain their function.