12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Conjunctivitis

Increased production of 12-hydroxyeicosatetraenoic acid [12(R)-HETE] and 12-hydroxyeicosatrienoic acid [12(R)-HETrE] positively correlates with the in vivo progression of ocular surface inflammation in rabbits. Tear film was collected from human subjects with inflamed eyes to determine whether these eicosanoids could be detected from endogenous sources.. Control and inflamed eyes were assessed and assigned a subjective inflammatory score. Tears were collected and extracted with an internal standard. Single-ion-monitoring gas chromatography-mass spectrometry (SIM-GC-MS) was performed to quantitate endogenous levels of 12-HETE and 12-HETrE.. 12-HETrE was detected in the tear film of both control and inflamed eyes, with the mean level being seven times higher in inflamed tears. 12-HETE was not detected in control tears and was detected in only 6 of 38 inflamed-eye tear samples.. The current findings demonstrate that the human eye produces detectable amounts of 12-HETrE, which is released into the tear flow. The increased levels of 12-HETrE associated with ocular surface inflammation suggest that this eicosanoid may contribute to inflammation of the ocular surface in humans.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Arachidonic Acid; Conjunctivitis; Eye Foreign Bodies; Gas Chromatography-Mass Spectrometry; Humans; Inflammation; Iridocyclitis; Keratitis; Keratitis, Herpetic; Keratoconjunctivitis; Tears

Two biologically active cytochrome P-450 arachidonate metabolites previously were characterized: 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) and 12(R)-hydroxy-5,8,14-eicosatrienoic acid (12(R)-DH-HETE), which are endogenously formed in the corneal epithelium. The functional activity of these novel metabolites mimics changes observed in hypoxic corneas. Therefore, the effect of hypoxic stress was examined on metabolite formation in rabbits fitted with polymethylmethacrylate contact lenses. Although applied lenses fit tightly to the rabbit cornea, mechanical irritation also may contribute to the ocular response. Contact lens-induced hypoxic stress stimulated endogenous formation of both 12(R)-HETE (a sodium, potassium adenosine triphosphatase inhibitor) and 12(R)-DH-HETE (a vasodilatory, chemotactic, and angiogenic factor) in a time-dependent manner. After 4 hr of contact lens wear, a 21-fold increase in endogenous 12(R)-HETE formation concomitant with an increase in corneal thickness was observed. After prolonged contact lens wear (144 hr), a 23-fold increase in endogenous 12(R)-DH-HETE formation was found, corresponding with the appearance of a marked conjunctival inflammation characterized by corneal neovascularization. The increased formation of these compounds was associated with time-dependent changes in corneal endothelial morphology. The ability of 12(R)-HETE and 12(R)-DH-HETE to mediate the clinical signs of corneal hypoxia suggest these metabolites may be potential mediators of contact lens complications that followed conditions of hypoxic stress and possibly mechanical irritation in this model.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 8,11,14-Eicosatrienoic Acid; Animals; Cell Count; Chromatography, High Pressure Liquid; Conjunctivitis; Contact Lenses; Cornea; Corneal Neovascularization; Cytochrome P-450 Enzyme System; Endothelium, Corneal; Epithelium; Hydroxyeicosatetraenoic Acids; Methylmethacrylates; Oxygen Consumption; Rabbits; Time Factors

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Aqueous Humor; Arachidonic Acids; Chemotaxis, Leukocyte; Conjunctiva; Conjunctivitis; Edema; Intraocular Pressure; Iris; Lipoxygenase; Prostaglandins; Rabbits