Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain‐derived neurotrophic factor

Abstract

Müller glia play an important role in maintaining retinal homeostasis, and brain-derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Müller cell activation, and to determine the extent to which BDNF affects the injury response of Müller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intravitreal injection of BDNF (5 microg). GFAP protein levels were normal at 1 day post-crush, but increased approximately 9-fold by day 3 and remained elevated over the 2-week period studied. Müller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24-h period post-crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Müller cell expression of either GS or GFAP in response to optic nerve injury.

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

“…7 A,C(ii)). GFAP is known to be expressed in Müller glia and astrocytes (Chen and Weber 2002). GFAP was found co-localized with GS in the Müller glial endfeet ( Fig.…”

“…It has already been shown that an upregulation of cytoskeletal proteins and downregulation of GS is associated with activated porcine Müller glia in culture (Hauck et al, 2003). In addition, decreased levels of GS in the Müller glial somata were observed following optic nerve crush (Chen and Weber 2002), which was interpreted as Müller glia initiating dedifferentiation in an attempt to replace dying cells. A reduction in GS could be additive to the already stressful environment in the rd10, as GS is known to be neuroprotective against retinal insult (Gorovits et al, 1997).…”

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

“…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. In the case of either diabetic retinopathy or optic nerve crush, there is no significant change in the levels of glutamine synthetase (Mizutani et al, 1998;Chen and Weber, 2002).…”

Stressor-dependent Alterations in Glycoprotein 130: Implications for Glial Cell Reactivity, Cytokine Signaling and Ganglion Cell Health in Glaucoma

“…As a general measure of glial reactivity, we examined immunolabeling intensity of the astrocyte marker GFAP and the Müller glia marker glutamine synthetase. An increase in the expression of these markers is associated with increased reactivity or activation of astrocytes and Müller glia in response to a variety of stressors in retina [37][38][39][40][41][42][43][44]. Since we evaluated overall labeling intensity, increases in GFAP or glutamine synthetase levels can be attributed to either increased expression on a per cell basis, which accompanies hypertrophy, or an increase in density.…”

“…Previous studies indicate that uptake and anterograde transport of CTB by RGCs is an early indicator of RGC decline [34][35][36]. Similarly, expression of GFAP by astrocytes and glutamine synthetase by Müller cells is altered in response to retinal damage, including glaucoma [37][38][39][40][41][42][43][44]. For our analysis in whole mount retina, we sampled 60x fields in the area between mid-central and mid-peripheral retina.…”