A CLOSED EYE CONTACT-LENS MODEL OF CORNEAL INFLAMMATION .2. INHIBITION OF CYTOCHROME-P450 ARACHIDONIC-ACID METABOLISM ALLEVIATES INFLAMMATORY SEQUELAE

Purpose. The authors have previously shown a marked increase in cornea l epithelial arachidonic acid metabolism to 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE) in a mode l of closed eye-contact lens wear. Their formation was predominantly c ytochrome P450-dependent and significantly correlated with inflammator y 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 eicosano ids as mediators of the inflammatory response to contact lens wear in the closed eye. Methods. Hydrogel contact lenses were soaked in stanno us chloride (100 mu g/ml) or vehicle and fitted to the rabbit eye in s tacked fashion (two lenses/eye), followed by a silk suture tarsorrhaph y of approximate to 90%. Eyes were analyzed over a 7-day period for in flammatory responses through slit lamp biomicroscopy, subjective infla mmatory scoring, ultrasonic pachymetry, and corneal epithelial [1-C-14 ]-arachidonic acid metabolism. Results. Closed eye-hydrogel contact le ns wear resulted in a progressive anterior surface inflammatory respon se. Coinciding with these events was a time-dependent increase in corn eal thickness and 12-HETE and 12-HETrE production rates by corneal epi thelial homogenates. Treatment of the lenses with stannous chloride (1 00 mu g/ml) significantly attenuated by day 7 the inflammatory score ( 56% decrease), corneal thickness (17% decrease), and 12-HETE and 12-HE TrE synthesis (77% and 71% decrease, respectively. Conclusions. This s tudy further substantiates the involvement of cytochrome P450, through the synthesis of 12-HETE and 12-HETrE, in the inflammatory response a ssociated with hydrogel contact lens wear in the closed eye. Thus, inh ibition of cytochrome P450, with subsequent decreases in 12-HETE and 1 2-HETrE, may attenuate the pathophysiologic response to contact lens w ear in the closed eye.