Fd Echevarria1, Cc Walker2, Sk Abella2, M Won2, Rm Sappington3. 1. Neuroscience Graduate Program, Vanderbilt University School of Medicine, 11425 Medical Research Building IV, Nashville, TN 37232-0654, USA ; Department of Ophthalmology and Visual Sciences (Vanderbilt Eye Institute), Vanderbilt University School of Medicine, 11425 Medical Research Building IV, Nashville, TN 37232-0654, USA. 2. Department of Ophthalmology and Visual Sciences (Vanderbilt Eye Institute), Vanderbilt University School of Medicine, 11425 Medical Research Building IV, Nashville, TN 37232-0654, USA. 3. Department of Ophthalmology and Visual Sciences (Vanderbilt Eye Institute), Vanderbilt University School of Medicine, 11425 Medical Research Building IV, Nashville, TN 37232-0654, USA ; Department of Pharmacology, Vanderbilt University School of Medicine, 11425 Medical Research Building IV, Nashville, TN 37232-0654, USA.
Abstract
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.
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.
Authors: M Narazaki; K Yasukawa; T Saito; Y Ohsugi; H Fukui; Y Koishihara; G D Yancopoulos; T Taga; T Kishimoto Journal: Blood Date: 1993-08-15 Impact factor: 22.113
Authors: Rachel A Fischer; Yuchen Zhang; Michael L Risner; Deyu Li; Yaqiong Xu; Rebecca M Sappington Journal: Adv Healthc Mater Date: 2018-06-25 Impact factor: 9.933
Authors: Gina N Wilson; Denise M Inman; Christine M Dengler Crish; Christine M Denger-Crish; Matthew A Smith; Samuel D Crish Journal: J Neuroinflammation Date: 2015-09-17 Impact factor: 8.322
Authors: D'Anne S Duncan; William M McLaughlin; Noah Vasilakes; Franklin D Echevarria; Cathryn R Formichella; Rebecca M Sappington Journal: J Clin Cell Immunol Date: 2017-05-24
Authors: Sean J Lee; D'Anne S Duncan; Franklin D Echevarria; William M McLaughlin; Jeremy B Hatcher; Rebecca M Sappington Journal: J Clin Exp Ophthalmol Date: 2015-10-27