Pregnenolone sulfate decreases intraocular pressure and changes expression of sigma receptor in a model of chronic ocular hypertension |
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Authors: | Xian Sun Fang Cheng Bo Meng Binbin Yang Wulian Song Huiping Yuan |
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Institution: | (1) Key Laboratory of Ophthalmology, Department of Ophthalmology, The 2nd Affiliated Hospital, Harbin Medical University, 246 Xuefu Road, Harbin, 150086, Heilongjiang, People’s Republic of China;(2) Department of Oncology, The 3rd Affiliated Hospital, Harbin Medical University, 150 Haping Road, Harbin, 150086, Heilongjiang, People’s Republic of China; |
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Abstract: | Sigma receptors are Ca2+-sensitive, ligand-operated receptor chaperones at the mitochondrion-associated endoplasmic reticulum membrane. This study
describes the effect of the sigma receptor 1 agonist pregnenolone sulfate on intraocular pressure (IOP) and sigma receptor
1 expression in rat retinas after chronic ocular hypertension. Chronic ocular hypertension was induced by occlusion of episcleral
veins. Retinal histological sections were obtained to determine inner plexiform layer thickness and the number of cell bodies
in the ganglion cell layer. Sigma receptor expression in rat retinas was analyzed by RT-PCR and Western blotting. Cauterization
caused IOP to increase >73%, and the pressure was maintained for 2 months. A time-dependent loss of ganglion cells and retinal
thickness occurred at elevated IOP. High IOP decreased sigma receptor 1 expression during the first week, but expression was
increased at 8 weeks. Injected pregnenolone significantly decreased IOP, prevented ganglion cell loss, protected inner plexiform
layer thickness, and increased sigma receptor 1 expression in episcleral vein-cauterized rats. Sigma receptors appear to be
neuroprotective and potential targets for glaucoma therapeutics. |
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