Signal transduction and gene expression in the eye: A contemporary view of the pro-inflammatory anti inflammatory and modulatory roles of Prostaglandins and other bioactive lipids

Eye tissues respond to physiological and pathophysiological stimuli by the activation of phospholipases and the consequent release from membrane phospholipids of biologically active metabolites. These rapid events have profound effects on long-term ocular physiology. Activation of phospholipase A(2) is the first step in the synthesis of two important classes of lipid second messengers, the eicosanoids and platelet-activating factor (PAF). PAF accumulates in the cornea in response to injury. It has been shown to stimulate metalloproteinase gene expression in the corneal epithelium, and is, thus, implicated in the extracellular matrix remodeling that accompanies wound healing and ulceration. PAF antagonists confer protection in animal models of acute and chronic anterior segment inflammation, and block the PAF-enhanced glutamate release from retina. The latter effect suggests a role for PAF in glaucomatous neuronal damage. The eicosanoids, in particular the prostaglandins, have long been implicated in the pathophysiology of ocular inflammation and there is pharmacological evidence for their role in the regulation of intraocular pressure. The induction by PAF of the inducible prostaglandin synthase in neurons and in the corneal epithelium provides a link between the actions of these two lipid second messengers. There may be thresholds of lipid second messenger concentrations which govern their activities as physiological, defensive, or harmful.