Purpose.The eicosanoid, 15-(S)-hydroxyeicosa-5Z, 8Z-11Z, 13E-tetraenoic acid (15-(S)-HETE), is known to stimulate production of mucin glycoprotein by airway epithelium. This study investigated the effect of 15-(S)-HETE on the mucin glycoprotein secretion by the corneal epithelium.Methods.To determine the effect of dose, corneas of anesthetized New Zealand White rabbits were treated with 50, 500, or 5,000 nM 15-(S)-HETE in artificial tears for 120 minutes. To determine the time to onset of the response, corneas were treated with 500 or 1,000 nM 15-(S)-HETE in balanced salt solution for periods ranging from 5 to 120 minutes. Corneas were fixed for electron microscopy in fixative containing 0.5% cetylpyridinium chloride (CPC) to stabilize the layer of mucin-like glycoprotein on the corneal surface. The mucin layer thickness was measured by image analysis of electron micrographs.Results.The layer of CPC-fixed mucin-like glycoprotein on the surface of control corneas was 0.46 ± 0.04 &mgr;m thick. After treatment with 15-(S)-HETE, the thickness of the mucin layer increased to 0.64 ± 0.1 &mgr;m at 50 or 5,000 nM HETE and as much as 1.02 ± 0.2 &mgr;m in response to 500 nM HETE. Mucin thickness reached a statistical maximum of 0.59 ± 0.1 &mgr;m after only 5 minutes of exposure to 500 or 1,000 nM HETE.Conclusions.Exposure of the cornea to 15-(S)-HETE causes a rapid-onset increase in the thickness of a layer of mucin-like glycoprotein on the surface of the corneal epithelium. This supports previous reports that corneal epithelial cells produce mucin and suggests that treatment with topical 15-(S)-HETE may be effective in treating ocular surface mucin deficiency in dry eye syndrome.