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Dorette Z Ellis, Linya Li, Yong H Park, Brett H Mueller, Hai-Ying Ma, Thomas Yorio, ; Sigma-1 Receptor Increases Mitochondrial Membrane Potential in Glucose and Oxygen deprived Retinal Ganglion Cells. . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4258.
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© ARVO (1962-2015); The Authors (2016-present)
Understanding the role of mitochondria in retinal ganglion cells (RGCs) is relevant to human disease, as studies showed mitochondrial abnormalities in primary open angle glaucoma patients. Recent studies in our laboratory demonstrated that glucose and oxygen deprivation (OGD) decreased mitochondrial movement in RGCs and sigma-1 receptors (σ-1r) agonists restored mitochondrial movement following OGD. This study determined the role of the σ-1r in regulating mitochondrial membrane potential in RGCs.
RGCs were isolated from rat pups and subjected to OGD in the presence or absence of σ-1r agonist and antagonist and AAV-σ-1r vector, used to increase σ-1r expression. Mitochondrial membrane potential was measured using JC1 dye. Caspase 3 and 7 activities were measured using luminescent assay kit.
OGD in RGCs resulted in decreased mitochondrial membrane potential when compared to normoxic RGCs. Addition of σ-1r agonists restored the mitochondrial membrane potential comparable to normoxic conditions while σ-1r antagonists abolished these effects. Overexpression of the σ-1r resulted in the restoration of RGCs’ health following OGD deprivation. Caspase activity was increased in response to ODG and decreased by σ-1r agonist, pentazocine and σ-1r overexpression.
These data suggest that σ-1r restores RGCs function following OGD; particularly mitochondrial function which is vital to the health of the cells.
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