September 1997
Volume 38, Issue 10
Free
Articles  |   September 1997
Alkali burn-induced synthesis of inflammatory eicosanoids in rabbit corneal epithelium.
Author Affiliations
  • M S Conners
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • F Urbano
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • C Vafeas
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • R A Stoltz
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • M W Dunn
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • M L Schwartzman
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Investigative Ophthalmology & Visual Science September 1997, Vol.38, 1963-1971. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M S Conners, F Urbano, C Vafeas, R A Stoltz, M W Dunn, M L Schwartzman; Alkali burn-induced synthesis of inflammatory eicosanoids in rabbit corneal epithelium.. Invest. Ophthalmol. Vis. Sci. 1997;38(10):1963-1971.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

PURPOSE: Alkali burning of the rabbit cornea is a well-established model for the study of anterior surface inflammation, neovascularization, and wound-healing processes. 12-hydroxyeicosanoids have been implicated as mediators of such responses. 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) is a lipoxygenase-derived arachidonate metabolite and 12(R)-hydroxyeicosatetraenoic acid (12[R]-HETE) is formed by a cytochrome P450 monooxygenase; both give rise to the potent angiogenic factor 12(R)-hydroxyeicosatrienoic acid (12[R]-HETrE). In this study, the authors correlate the pattern of their synthesis in the corneal epithelium with the inflammatory response after alkali injury. METHODS: New Zealand albino rabbits were anesthetized and alkali burns created with 10-mm filter paper discs (1 N NaOH for 2 minutes). Corneas were then rinsed; 1 to 7 days later, corneal epithelium was scraped and used to assess 14C-arachidonic acid conversion to 12-HETE and 12-HETrE enantiomers in the presence of NADPH by chiral high-pressure liquid chromatography. The inflammatory response secondary to the alkali burn was quantified through area measurements of reepithelialization and neovascularization. RESULTS: Alkali burn induced a time-dependent production of corneal epithelial 12-HETE and 12-HETrE. A marked increase in 12-HETE and 12-HETrE synthesis was evident at day 2 (from 22 +/- 7 to 139 +/- 22 ng/hour) after injury, increasing to 800 +/- 68 ng/hour at day 7. Chiral analysis revealed a time-dependent synthesis of the R and S enantiomers of 12-HETE (24% R, 76% S) and 12-HETrE (72% R, 28% S). Total arachidonate metabolism, as well as the formation of 12(R)-HETrE, correlated with the area of neovascularization (P < 0.01 and P < 0.02, respectively). CONCLUSIONS: The results demonstrate that surviving and regenerating epithelium has an increased capacity of synthesizing 12(S)-HETE and 12(R)-HETE and that maximal production of 12(R)-HETrE, a known direct and indirect angiogenic factor, coincides with neovascularization in this model. Thus, the lipoxygenase and cytochrome P450-dependent activities increased in a time-dependent manner, indicating the potential involvement of both pathways in the inflammatory response to alkali burn. The formation of significant quantities of 12(R)-HETE and 12(R)-HETrE is a novel finding in this alkali injury model.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×