A closed eye contact lens model of corneal inflammation. Part 1: Increased synthesis of cytochrome P450 arachidonic acid metabolites.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Conners
M S
MS
Department of Pharmacology, New York Medical College Valhalla, 10595, USA.
Stoltz
R A
RA
Webb
S C
SC
Rosenberg
J
J
Dunn
M W
MW
Abraham
N G
NG
Laniado-Schwartzman
M
M
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003262:Contact Lenses, Extended-Wear / Q000009:adverse effects; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D015715:Corneal Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005143:Eyelids / Q000601:surgery*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D007634:Keratitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011817:Rabbits; D013997:Time Factors
D006893:Hydroxyeicosatetraenoic Acids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003577:Cytochrome P-450 Enzyme System