Altered expression of 3α-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes

O. A. Agapova, P. Yang, W. H. Wang, D. A. Lane, A. F. Clark, B. I. Weinstein, M. R. Hernandez

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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 we demonstrated that in glaucomatous human optic nerve heads, increased expression of 3α-HSD was localized to reactive astrocytes in the lamina cribrosa. Similar, 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. Our findings of increased expression of 3α-HSDs in glaucomatous optic nerve head astrocytes offer new insights into possible roles for neurosteroids in the pathophysiology of glaucoma.

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalNeurobiology of Disease
Volume14
Issue number1
DOIs
StatePublished - Oct 2003

Keywords

  • 3α-HSD
  • AKR1C1
  • AKR1C2
  • AKR1C3
  • Glaucoma
  • Human
  • Immunohistochemistry
  • In situ hybridization
  • Monkey
  • Neurosteroid
  • Optic nerve head astrocytes
  • Optic nerve transection
  • Real-time RT-PCR

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