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Mol Biol Rep (2012) 39:66076614 DOI 10.1007/s11033-012-1491-5
Pregnenolone sulfate decreases intraocular pressure and changes expression of sigma receptor in a model of chronic ocular hypertension
Xian Sun Fang Cheng Bo Meng
Binbin Yang Wulian Song Huiping Yuan
Received: 27 July 2011 / Accepted: 24 January 2012 / Published online: 7 February 2012 Springer Science+Business Media B.V. 2012
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 rst week, but expression was increased at 8 weeks. Injected pregnenolone signicantly 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 neuro-protective and potential targets for glaucoma therapeutics.
Keywords Sigma receptor 1 Intraocular pressure
Retinal ganglion cell Neuroprotection Glaucoma
Introduction
Glaucoma, is a progressive optic neuropathy often associated with increased intraocular pressure (IOP) and characterized by progressive death of retinal ganglion cells (RGCs) and consequent deterioration of the visual eld [1, 2]. It is important to identify an ideal drug that can both lower IOP and provide neuroprotection. Sigma receptor 1 has been studied extensively in the central nervous system and is overly abundant in ocular tissues such as the lacrimal gland, retina, iris-ciliary body, cornea, and lens [3, 4]. Because sigma receptor 1 regulates intracellular calcium levels, prevents activation of pre-apoptotic genes [5], and decreases glutamate accumulation and its express in iris-ciliary body and trabecular meshwork (it will be published in our another paper) [6]. We deduce that sigma receptor 1 should have some roles on IOP and neuroprotection. However, in vivo and in vitro data...