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Abstract #9698 Published in IGR 5-3
Altered expression of 3α-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes
Agapova OA; Yang P; Wang WH; Lane DA; Clark AF; Weinstein BI; Hernandez MRNeurobiology of Disease 2003; 14: 63-73
3α-Hydroxysteroid dehydrogenase (3α-HSD) isoforms (AKR1C1-AKR1C4) are aldo-keto reductases that metabolize steroids and other substances in many tissues including the CNS. Here it is demonstrated that, in glaucomatous human optic nerve heads, increased expression of 3α-HSD was localized to reactive astrocytes in the lamina cribrosa. Similarly, optic nerve head astrocytes exhibited increased expression of 3α-HSD in response to elevated intraocular pressure in a monkey model of experimental glaucoma, but not in monkeys with unilateral optic nerve transection. In vitro, glaucomatous optic nerve head astrocytes expressed higher levels of AKR1C1, AKR1C2, and AKR1C3 mRNA, than normal astrocytes, with significant differential increase of AKR1C2 expression, and exhibited higher enzymatic activity forming 3α-androstanediol a well-recognized neurosteroid. Normal astrocytes exposed to elevated hydrostatic pressure selectively increased AKR1C2 expression. These findings of the increased expression of 3α-HSDs in glaucomatous optic nerve head astrocytes offer new insights into possible roles for neurosteroids in the pathophysiology of glaucoma.
Dr. M.R. Hernandez, Department of Ophthalmology/Visual Sciences, Washington University School of Medicine, Box 8096, 660 S Euclid Avenue, St Louis, MO 63110, USA
Classification:
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
