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Metabolism of arachidonic acid in the retina and retinal pigment epithelium: biological effects of oxygenated metabolites of arachidonic acid.

Most of the research on AA metabolites in the eye has been concerned with the role of prostaglandins in ocular inflammations. For example, it has been postulated that cystoid macular edema (CME) is due to accumulation of prostaglandins produced after cataract surgery and that indomethacin prevents the development of CME (Tennant, 1976; Milch and Yannuzzi, 1987). It is not known if the retina is the source of these prostaglandins. Cyclooxygenase and lipoxygenase activities have been demonstrated in the retina. In this chapter, evidence is presented indicating that eicosanoids can also be involved in retinal neurotransmission and cell to cell interaction. The mammalian retina contains a relatively large amount of AA esterified to membrane phospholipids. A release of AA takes place in the retina under various experimental conditions, e.g., anoxia, K+ polarization, and light exposure. This release of AA, a prerequisite for eicosanoid syntheses, is produced by phospholipases and lipases, some of which are regulated by receptor-mediated G-proteins. Prostaglandins can act as modulators of postsynaptic responses; some can also alter the electroretinographic response, for example PGD2 selectively increases during light stimulation. An increase in LTC4 occurs in the neural retina after Ca+ ionophore stimulation and an increase in LTC4 released from retinal pigment epithelium occurs after light onset before massive shedding, suggesting an involvement of 5-lipoxygenase metabolites in the initial steps of ROS phagocytosis. Although great advances have been made regarding the function of eicosanoids in the central nervous system (of which the retina is a constitutive part), it is yet a very difficult task to determine to what extent eicosanoids are involved in the action of neurotransmitters and whether they may act as neuromodulators. This is due to the complexity of the synaptic circuitry of the retina, which makes it difficult to define their sources and physiological significance.