Pregnenolone sulfate decreases intraocular pressure and changes expression of sigma receptor in a model of chronic ocular hypertension.
Sigma receptors are Ca(2+)-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.
Key Laboratory of Ophthalmology, Department of Ophthalmology, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
Xian
X
Sun
Fang
F
Cheng
Bo
B
Meng
Binbin
B
Yang
Wulian
W
Song
Huiping
H
Yuan
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D007429:Intraocular Pressure / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011284:Pregnenolone / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017480:Receptors, sigma / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D000097605:Sigma-1 Receptor
D018696:Neuroprotective Agents; D011284:Pregnenolone; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C018370:pregnenolone sulfate