The ocular effects of eicosanoids and other autacoids: historic background and the need for a broader perspective

Great progress has been made in describing the synthesis of most known eicosanoids by ocular tissues. This progress has included identification of the spectrum of eicosanoids synthesized by different ocular tissues of different species, as well as comparisons of the relative proportion of individual eicosanoids produced by ocular tissues of different species. In contrast to this wealth of information, the lack of antagonists that are specific to individual eicosanoids has greatly hindered efforts to determine the specific ocular functions of each member of this family of autacoids. Furthermore, the absence of high-affinity ligands that are specific for individual eicosanoid receptors has greatly limited our ability to classify these receptors and to assign specific eicosanoid effects to specific cell types. In the early years of ocular PG research, the lack of recognition of the existence of parallel pathways of arachidonic acid metabolism and the lack of appreciation of the effects of some other autacoids--most notably the recently discovered neuropeptides--led to the premature conclusion that PGs have mediatory roles in a number of ocular pathophysiological responses. More recent studies have demonstrated that some ocular effects, such as chemotaxis, that were first attributed to classical PGs of the E and F type are actually mediated by eicosanoids synthesized by the lipoxygenase pathway, whereas other ocular responses, at least in some species, are mediated by various neuropeptides. These neuropeptides can be released by the same stimuli that cause the release of arachidonic acid. Furthermore, interpretation of the ocular effects of eicosanoids as well as neuropeptides has been complicated by large species differences in the effects of these autacoids on intraocular tissues. Among mammalian species, the rabbit eye and the primate eye may represent opposite extremes with respect to the extent of their responses to irritation and trauma, as well as with respect to their responses to some autacoids, especially eicosanoids and neuropeptides. In spite of these differences, the rabbit remains the animal most widely used in eye research. Consequently, many of the findings reviewed in this volume are also based on studies done only on rabbits. However, in view of the foregoing, we must resist the temptation to extrapolate to primates results obtained only from studies of rabbit eyes.(ABSTRACT TRUNCATED AT 400 WORDS)