Figure 1.

Hypothesized model of chronic ocular surface inflammation in dry eye. ω-3 and ω-6 polyunsaturated fatty acids are released into the tear film as part of meibum and/or from the ocular surface epithelium in response to injury from dessicating stress. Cyclooxygenases and lipoxygenases are expressed on the ocular surface by corneal epithelial cells and resident polymorphonuclear leukocytes. The ω-6 species, AA, is a substrate for cyclooxygenases and lipoxygenases and is converted to several classes of proinflammatory eicosanoids. In contrast, the ω-3 species, DHA and EPA, are also substrates for 15-lipoxygenase and 5-lipoxygenase, but are converted to several classes of proresolving, anti-inflammatory, and neuroprotective mediators. The formation of proinflammatory and proresolving lipid mediators regulates activation of effector cells on the ocular surface. In healthy eyes, proresolving lipid mediators counteract the eicosanoids and promote speedy resolution of inflammation. In dry eye, metabolic deficiency of ω-3 species leads to underproduction of proresolving lipid mediators and a state of chronic nonresolving inflammation on the ocular surface.