WHAT DO RETINAL MULLER (GLIAL) CELLS DO FOR THEIR NEURONAL SMALL SIBLINGS

Muller (radial glial) cells are the predominant glia of the vertebrate retina. They arise, together with rod photoreceptor cells, bipolar cells, and a subset of amacrine cells, from common precursor cells during a late proliferative phase. One Muller cell and a species-specific number of such neurons seem to form a columnar unit within the retinal tissue. In contrast, 'extracolumnar neurons' (ganglion cells, cone photoreceptor cells, horizontal cells, and another subset of amacrine cells) are born and start differentiation before most Muller cells are generated. It may be essential for such neurons to develop metabolic capacities sufficient to support their own survival, whereas late-born ('columnar') neurons seem to depend on a nursing function of their 'sisterly' Muller cell. Thus, out of the cell types within a retinal column it is exclusively the Muller cell that possesses the enzymes for glycogen metabolism. We present evidence that Muller cells express functional insulin receptors. Furthermore, isolated Muller cells rapidly hydrolyse glycogen when they are exposed to an elevated extracellular K+ion concentration, a signal that is involved in the regulation of neuronal-glial metabolic cooperation in the brain. Muller cells are also thought to be essential for rapid and effective retinal K+ homeostasis. We present patch-clamp measurements on Muller cells of various vertebrate species that all demonstrate inwardly rectifying K+ channels; this type of channel is well-suited to mediate spatial buffering currents. A mathematical model is presented that allows estimation of Muller cell-mediated K+ currents. A simulation analysis shows that these currents greatly limit lateral spread of excitation beyond the borders of light-stimulated retinal columns, and thus help to maintain visual acuity.