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

Abstract

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.

Dysfunction of Retinal Cell and Optic Nerve by Continuous Cerebroventricular Infusion of Glucosamine

“…There is an interesting report that immunoprecipitation of vimentin from E9 whole brain lysates confirmed O-GlcNAcylation of vimentin but not in neurons during brain development (Farach and Galileo, 2008). This is in consistent with the observation that the mRNA for intermediate filament proteins is exported from the cell body vitread to the end foot, and that the intermediate filament cytoskeleton expands from an initial growth region that exists there (Ekstrom et al, 1988;Sarthy and Fu, 1989;Erickson et al, 1992). Muller cells can proliferate, migrate, hypertrophy and shift the location of their nuclei.…”

Regeneration of Inner Retinal Neurons after Intravitreal Injection of Ouabain in Zebrafish

“…Most retinal injuries increase GFAP expression (Sarthy and Fu, 1989;Iandiev et al, 2006;Raymond et al, 2006;Xue et al, 2006), yet, surprisingly, ouabain damage decreased GFAP expression between 1 and 21 dpi (Fig. 8).…”

“…A sensitive, nonspecific response to a wide variety of retinal insults is an increase in the expression of intermediate filament protein GFAP (Sarthy and Fu, 1989;Iandiev et al, 2006;Raymond et al, 2006;Xue et al, 2006). In contrast, a change in glutamine synthetase expression appears to depend on the type of retinal damage that is sustained , with glutamine synthetase levels decreasing in response to photoreceptor cell damage and increasing under conditions of hepatic retinopathy.…”

Leukemia Inhibitory Factor Extends the Lifespan of Injured PhotoreceptorsIn Vivo

“…One of the most common response to retinal injury is the upregulation of the intermediate filament protein GFAP in Muller glia cells (Sarthy and Fu, 1989;Lewis and Fisher, 2003;Nakazawa et al, 2007). This is also evident during the degenerative process in the retina of the VPP mouse (Fig.…”