Transcriptional Activation of an Intermediate Filament Protein Gene in Mice with Retinal Dystrophy

We are interested in understanding neuronal interactions, that regulate expression of specific genes in glial cells in the nervous system. In the normal mouse retina, the glial intermediate filament protein (GFAP) is not detectable in Müller cells, the predominant glial cells in the retina. Photoreceptor degeneration resulting from retinal degeneration (rd) mutation or environmental light damage, however, leads to the appearance of GFAP in Müller cells. We have investigated the mechanism underlying GFAP accumulation in these retinas. Western blotting analysis, steady-state mRNA level comparisons, and nuclear run-on assays show that transcription of the GFAP gene is activated in these retinas. In situ hybridizations with retinal sections and solitary Müller cells establish that GFAP mRNA levels are elevated in Müller cells. These results show that disruption of neuron–glia interactions resulting from photoreceptor degeneration leads to activation of the GFAP gene in glial cells of mice with retinal dystrophy. The functional significance of this glial response and the need for GFAP expression remain to be understood.