Morphology of Astrocytes in a Glaucomatous Optic Nerve

Lye-Barthel, Ming; Sun, Daniel; Jakobs, Tatjana C.

doi:10.1167/iovs.12-10109

Cited by 96 publications

(93 citation statements)

References 27 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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. Both hypertrophy and changes in cell density are hallmarks of glial reactivity and have been described in various retinal diseases, including glaucoma [5,[52][53][54][55][56][57][58]. In all groups, we noted instances of changes in expression/cell and, for astrocytes, differences in cell density.…”

Section: Discussionsupporting

confidence: 52%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 52%

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

View full text Add to dashboard Cite

show abstract

“…Changes in astrocyte morphology, such as enlargement of the cell body and processes, as well as up-regulation of cytoskeletal and extracellular matrix proteins, have been observed in the retina and ONH in human glaucoma (Wang et al 2002;Inman and Horner 2007;Hernandez et al 2008;Kompass et al 2008;Nikolskaya et al 2009). Several studies have demonstrated that this reactivity and remodeling of astrocytes, and the increased deposition of extracellular matrix occur in early stages of experimental glaucoma (Johnson and Morrison 2009;Howell et al 2011a;Johnson et al 2011;Lye-Barthel et al 2013;Qu and Jakobs 2013). In fact, just a short term elevation of IOP induces rapid and reversible morphological…”

Section: Activation Of Astrocytes and Microglia In The Optic Nerve Hementioning

confidence: 99%

The Complex Role of Neuroinflammation in Glaucoma

Soto

Howell

2014

Cold Spring Harbor Perspectives in Medicine

187

156

View full text Add to dashboard Cite

“…72 In a mouse model of glaucoma, astrocytes at the ONH become thicker in animals with moderate to severe disease and exhibited a simplified arbor network. 73 In human glaucoma patients, astrocytes express the cytokine TNFα and its receptor type 1 (TNF-R1) in the ONH. 58,74 Although the consequence of TNFα production is complicated and has been linked to neurodegeneration and neuroprotection, 58,75-81 astrocytes appear to be the primary producer of this cytokine in the ONH.…”

Section: Astrocytesmentioning

confidence: 99%