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Kathryn E Bollinger, Barbara A Mysona, graydon gonsalvez, Manuela Bartoli, Sylvia B Smith, Jing Zhao; Sigma 1 Receptor Activation Enhances Optic Neve Head Astrocyte Reactivity Under Conditions of Cellular Stress. Invest. Ophthalmol. Vis. Sci. 2020;61(7):691.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of this work was to evaluate the effects of the sigma 1 receptor (S1R) on reactivity of optic nerve head astrocytes (ONHAs). Stimulation of S1R is neuroprotective in models of CNS and retinal neurodegeneration. Since S1R is expressed in both neurons and glia, we aimed to examine how S1R activation affects ONHA reactivity under conditions of cellular stress.
Methods: ONHAs were derived from wild type (WT) and S1R knockout (KO) mice. Cell cultures were subjected to oxygen glucose deprivation (OGD at 0.5% O2), then treated with the S1R agonist, (+)-pentazocine ((+)-PTZ) at a concentration of 10µM. Astrocyte reactivity responses were evaluated including cell migration and GFAP expression. In addition, activation of molecules that regulate ONHA reactivity was evaluated. This included measurement of Signal Transducer and Activator of Transcription 3 (STAT3) and Nuclear Factor kappa B (NF-kB) activation levels using immunoblotting.
Baseline treatment of WT ONHAs with (+)-PTZ showed no significant change in either GFAP levels, STAT3 activation or NF-kB(p65) activation. However, baseline (+)-PTZ treatment led to an S1R-dependent increase in astrocyte migration. Exposure of WT and KO ONHAs to OGD led to increased GFAP levels. The OGD-induced increase in GFAP levels was significantly enhanced in ONHAs derived from WT mice but not in astrocytes derived from KO animals. OGD exposure also increased STAT3 and NF-kB(p65) activation in WT ONHAs. Treatment of OGD-exposed WT ONHAs with (+)-PTZ enhanced STAT3 activation but attenuated NF-kB(p65) activation.
Stimulation of S1R within ONHAs led to an increase in measures of astrocyte reactivity. Under conditions of OGD-mediated stress, S1R activation enhanced aspects of reactivity. These effects may increase neuroprotective properties of ONHAs.
This is a 2020 ARVO Annual Meeting abstract.
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