HPETE, AN ARACHIDONIC-ACID METABOLITE, INDUCES APOPTOSIS IN THE RAT RETINA IN-VITRO

Background. Apoptosis is a gene-regulated mode of cell death which gai ns increasing importance in retinal pathologies such as retinitis pigm entosa, retinal detachment and proliferative vitreoretinopathy. A bett er understanding of the regulation of apoptosis could imply the means to reduce photoreceptor cell death and thereby provide therapeutic str ategies to influence the time course of retinal diseases. Previous stu dies in our laboratory demonstrated that light induces apoptosis in th e rat retina in vivo as a function of light dose. In several cell syst ems, oxidative stress including oxygenated metabolites of arachidonic acid (AA) was found to evoke apoptosis. We have observed a light-elici ted release of AA and the subsequent formation of its metabolites in t he rat retina. Therefore, AA and its metabolites appeared to be suitab le candidates for the induction of apoptosis during light exposure. Ma terials and methods. Isolated rat retinas were incubated for 60, 120 a nd 180 min, respectively, with and without the addition of 30 mu mol 5 S-hydroperoxyeicosatetraenoic acid (5-HPETE). Retinas were then proces sed for light- and electron microscopy and examined for the morphologi cal signs of apoptosis. The rate of apoptosis in the outer nuclear lay er was assessed quantitatively. Results. 5S-HPETE induces apoptosis of photoreceptors in the rat retina in vitro. Quantitative analysis reve aled a significant increase: in the rate of apoptosis of 5S-HPETE-trea ted retinas when compared to untreated controls. Conclusion Arachidoni c acid metabolites released upon light exposure may represent messenge r candidates for apoptosis in the retina.