12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Corneal-Edema

To characterize a model of contact lens-induced corneal inflammation in the closed eye, with respect to inflammatory parameters and the metabolism of arachidonic acid by homogenates of the corneal epithelium.. Rabbit eyes were fitted with extended wear etafilcon A (58% water) hydrogel contact lenses in stacked fashion (two lenses per eye), followed by a silk suture tarsorrhaphy of approximately 90%. The anterior surface was analyzed over a 9-day period for inflammatory events through slit lamp biomicroscopy, subjective inflammatory scoring, corneal pachymetry, and corneal epithelial [1-(14)C]-arachidonic acid metabolism.. Hydrogel contact lens wear in the closed eye resulted in a progressive anterior surface inflammatory response correlated over time (r = 0.999). Central corneal thickness progressively increased and was also correlated to the inflammatory score (r = 0.995). [1-(14)C]-arachidonic acid metabolism by homogenates of the corneal epithelium resulted in the time-dependent formation of two major products, 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE). Correlations were established between the synthesis of 12-HETE and 12-HETrE, the subjective inflammatory score (r = 0.963) and the progressive increase in corneal thickness (r = 0.971), over 9 days.. With this model of contact lens wear, eicosanoid synthesizing capacity of the corneal epithelium showed a time-dependent increase in the production of 12-HETE and 12-HETrE strongly correlating to the in situ inflammatory response. The relationship between 12-HETE and 12-HETrE synthesis and the degree of anterior surface inflammation implicate these eicosanoids, among others, as mediators of the inflammatory response to hydrogel contact lens wear in the closed eye.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Chromatography, High Pressure Liquid; Contact Lenses, Extended-Wear; Cornea; Corneal Edema; Cytochrome P-450 Enzyme System; Disease Models, Animal; Epithelium; Eyelids; Hydroxyeicosatetraenoic Acids; Keratitis; Male; Rabbits; Time Factors

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.. 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.. 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).. 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.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Contact Lenses, Extended-Wear; Cornea; Corneal Edema; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Disease Models, Animal; Drug Delivery Systems; Epithelium; Eyelids; Hydroxyeicosatetraenoic Acids; Keratitis; Male; Rabbits; Time Factors; Tin Compounds