Reactive changes of retinal astrocytes and Müller glial cells in kainate‐induced neuroexcitotoxicity

Chang, Min Lin; Wu, Ching Hsiang; Jiang-Shieh, Ya Fen; Shieh, Jeng-Yi; Wen, Congcong

doi:10.1111/j.1469-7580.2006.00671.x

Cited by 111 publications

(86 citation statements)

References 40 publications

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“…These reports suggested that the decrease in the number of cells observed in the GCL after intravitreal glutamate injections might have resulted from a loss of amacrine cells and from a lack of trophic support for RGCs. KA induces activation of retinal astrocytes and Müller cells, which reflects a metabolic change of the cells in response to degenerative changes of their neighboring neurons, which may give evidence of repair process in KA-induced damage [5]. Previous studies have shown that Pax6 mRNA was expressed during development of the mouse retina and in the adult mouse retina [21] and was upregulated during retinal regeneration [13].…”

Section: Discussionmentioning

confidence: 99%

Expression of Small Leucine-Rich Proteoglycans in the Developing Retina and Kainic Acid-Induced Retinopathy in ICR Mice

Ali

Hosaka

Uehara

2011

The Journal of Veterinary Medical Science

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ABSTRACT. The aim of this study was to determine the developmental changes of small leucine-rich proteoglycans (PGs), decorin, biglycan and fibromodulin, in ICR mouse retinas and to elucidate their role in the adult retina using kainic acid (KA)-induced retinal degeneration model. Retinas of prenatal, postnatal and adult mice were collected for histological and immunohistochemical staining to investigate the changes in distribution of these PGs. Decorin-and fibromodulin-immunostainings were diffusely distributed at prenatal and early postnatal stages and were stronger in the adult retina. However, biglycan was moderately distributed in the prenatal and early postnatal stages and was faint in the adult retina. Retinas were collected at 1, 3 and 7 days after intravitreal injection of KA. Retinas of KA injected eyes underwent shrinkage accompanied by serious damage in the inner layers. Decorin and fibromodulin were upregulated in the inner retinal layers of KA-injected eyes compared to the normal ones. Our results suggest that decorin and fibromodulin play key roles in retinal differentiation, and contribute to the retinal damage and repair process. However, biglycan may have no or only a limited role in the mouse retinal development or repair process.KEY WORDS: biglycan, decorin, fibromodulin, kainic acid, retinal development and damage.

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Section: Discussionmentioning

confidence: 99%

Expression of Small Leucine-Rich Proteoglycans in the Developing Retina and Kainic Acid-Induced Retinopathy in ICR Mice

Ali

Hosaka

Uehara

2011

The Journal of Veterinary Medical Science

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“…This serum was also specific for GFAP on immunoblots in extracts from the mouse spinal cord 24) and rat retina 25) .…”

Section: Glial Fibrillary Acidic Protein (Gfap)mentioning

confidence: 95%

Chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase in the rat optic nerve: An immunohistochemical study

Kawano

2015

Okajimas Folia Anat. Jpn.

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Summary: An immunohistochemical analysis of the chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) was conducted in the rat optic nerve. The optic nerve has been divided into 3 regions: the intraretinal, unmyelinated, and myelinated regions. However, it currently remains unclear whether the chemoarchitecture of GFAP and GS is homogeneously organized, especially in the myelinated region. The intraretinal region was divided into intraretinal regions 1 (i1) and 2 (i2). GFAP immunoreactivity was very strong in the i2 and unmyelinated regions, and strong in the i1 region. GS immunoreactivity was moderate in the i1 and i2 regions, and weak in the unmyelinated region. The myelinated region was separated into myelinated regions 1 (m1) and 2 (m2). In the m1 region, GFAP immunoreactivity was strong and GS immunoreactivity was moderate; however, GFAP immunoreactivity was moderate and GS immunoreactivity was weak in the m2 region. Thus, the chemoarchitecture was heterogeneously organized in the myelinated region, with the i1, i2 and m1 regions being the main GS distribution sites. Moreover, most GS-immunoreactive glial cells were oligodendrocytes in the myelinated region. Since GS is a key enzyme in glutamate metabolism, these results may facilitate future investigations for a clearer understanding of glutamate metabolism.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Stressor-dependent Changes In Gp130 Are Accompanied By Altermentioning

confidence: 99%

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

Echevarria

et al. 2013

J Clin Exp Ophthalmol

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Objective: The interleukin-6 (IL-6) family of cytokines is associated with retinal ganglion cell (RGC) survival and glial reactivity in glaucoma. The purpose of this study was to evaluate glaucoma-related changes in glycoprotein-130 (gp130), the common signal transducer of the IL-6 family of cytokines, as they relate to RGC health, glial reactivity and expression of IL-6 cytokine family members. Methods:For all experiments, we examined healthy retina (young C57), aged retina (aged C57), retina predisposed to glaucoma (young DBA/2) and retina with IOP-induced glaucoma (aged DBA/2). We determined retinal gene expression of gp130 and IL-6 family members, using quantitative PCR, and protein expression of gp130, using multiplex ELISA. For protein localization and cell-specific expression, we performed co-immunolabeling for gp130 and cell type-specific markers. We used quantitative microscopy to measure layer-specific expression of gp130 and its relationships to astrocyte and Müller glia reactivity and RGC axonal transport, as determined by uptake and transport of cholera toxin β-subunit (CTB).Results: Gene expression of gp130 was elevated with all glaucoma-related stressors, but only normal aging increased protein levels. In healthy retina, gp130 localized primarily to the inner retina, where it was expressed by astrocytes, Müller cells and RGCs. Layer-specific analysis of gp130 expression revealed increased expression in aging retina and decreased expression in glaucomatous retina that was eccentricity-dependent. These glaucoma-related changes in gp130 expression correlated with the level of GFAP and glutamine synthetase expression, as well as axonal transport in RGCs. The relationships between gp130, glial reactivity and RGC health could impact signaling by many IL-6 family cytokines, which exhibited overall increased expression in a stressor-dependent manner.Conclusions: Glaucoma-related stressors, including normal aging, glaucoma predisposition and IOP-induced glaucoma, differentially alter expression of gp130 and these alterations have direct implications for astrocyte and Müller glia reactivity, RGC health and cytokine signaling.

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Reactive changes of retinal astrocytes and Müller glial cells in kainate‐induced neuroexcitotoxicity

Cited by 111 publications

References 40 publications

Expression of Small Leucine-Rich Proteoglycans in the Developing Retina and Kainic Acid-Induced Retinopathy in ICR Mice

Expression of Small Leucine-Rich Proteoglycans in the Developing Retina and Kainic Acid-Induced Retinopathy in ICR Mice

Chemoarchitecture of glial fibrillary acidic protein (GFAP) and glutamine synthetase in the rat optic nerve: An immunohistochemical study

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

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