April 1995
Volume 36, Issue 5
Free
Articles  |   April 1995
A closed eye contact lens model of corneal inflammation. Part 2: Inhibition of cytochrome P450 arachidonic acid metabolism alleviates inflammatory sequelae.
Author Affiliations
  • M S Conners
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • R A Stoltz
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • K L Davis
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • M W Dunn
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • N G Abraham
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • R D Levere
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
  • M Laniado-Schwartzman
    Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Investigative Ophthalmology & Visual Science April 1995, Vol.36, 841-850. doi:
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    • Get Citation

      M S Conners, R A Stoltz, K L Davis, M W Dunn, N G Abraham, R D Levere, M Laniado-Schwartzman; A closed eye contact lens model of corneal inflammation. Part 2: Inhibition of cytochrome P450 arachidonic acid metabolism alleviates inflammatory sequelae.. Invest. Ophthalmol. Vis. Sci. 1995;36(5):841-850.

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Abstract

PURPOSE: The authors have previously shown a marked increase in corneal epithelial arachidonic acid metabolism to 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE) in a model of closed eye-contact lens wear. Their formation was predominantly cytochrome P450-dependent and significantly correlated with inflammatory score and corneal thickness. In the current study, the authors used stannous chloride to inhibit the epithelial cytochrome P450-dependent synthesis of 12-HETE and 12-HETrE to assess the role of these eicosanoids as mediators of the inflammatory response to contact lens wear in the closed eye. METHODS: Hydrogel contact lenses were soaked in stannous chloride (100 micrograms/ml) or vehicle and fitted to the rabbit eye in stacked fashion (two lenses/eye), followed by a silk suture tarsorrhaphy of approximately 90%. Eyes were analyzed over a 7-day period for inflammatory responses through slit lamp biomicroscopy, subjective inflammatory scoring, ultrasonic pachymetry, and corneal epithelial [1-14C]-arachidonic acid metabolism. RESULTS: Closed eye-hydrogel contact lens wear resulted in a progressive anterior surface inflammatory response. Coinciding with these events was a time-dependent increase in corneal thickness and 12-HETE and 12-HETrE production rates by corneal epithelial homogenates. Treatment of the lenses with stannous chloride (100 micrograms/ml) significantly attenuated by day 7 the inflammatory score (56% decrease), corneal thickness (17% decrease), and 12-HETE and 12-HETrE synthesis (77% and 71% decrease, respectively). CONCLUSIONS: This study further substantiates the involvement of cytochrome P450, through the synthesis of 12-HETE and 12-HETrE, in the inflammatory response associated with hydrogel contact lens wear in the closed eye. Thus, inhibition of cytochrome P450, with subsequent decreases in 12-HETE and 12-HETrE, may attenuate the pathophysiologic response to contact lens wear in the closed eye.

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