EFFECTS OF ENHANCED EXTRACELLULAR AMMONIA CONCENTRATION ON CULTURED MAMMALIAN RETINAL GLIAL (MULLER) CELLS

Muller (glial) cells of the neonatal rabbit retina were cultured as co nfluent monolayers and exposed to enhanced concentrations of ammonia ( 0.25, 0.5, 1, 3, 7, and 10 mM) in medium for various periods (30 min t o 10 d). This caused, in a time- and dose-dependent manner, similar ch anges in the Muller cells as had previously been described in cultured astrocytes. The most conspicuous events were 1) an increasing size of cell nuclei, 2) an accumulation of phagocytotic vacuoles, and 3) a re arrangement of intermediate filaments. 4) A considerable number of cel ls died when higher ammonia concentrations were applied for more than 1 h. Simultaneous application of dibutyryl-cyclic adenosine monophosph ate (dBcAMP) prevented almost completely both the increase in cell nuc leus size and the changes of intermediate filaments, but only partly t he early cell death of a subpopulation of cells, and the accumulation of phagocytotic vacuoles. Further changes evoked by enhanced ammonia c oncentration were 5) an accumulation of lipofuscin-like material (''fa tty degeneration'') revealed by lipophilic stain, 6) reduced immunorea ctivity for cathepsin D, and increased immunoreactivity for 7) glial f ibrillary acidic protein, 8) glutamine synthetase, and 9) bcl-2 protoo ncogene protein. These findings are discussed in respect to the possib le underlying pathophysiological mechanisms. (C) 1995 Wiley-Liss, Inc.