Increased levels of leukotriene C4in retinal pigment epithelium are correlated with early events in photoreceptor shedding inXenopus laevis

Abstract

The levels of 5-lipoxygenase products of arachidonic acid, leukotriene (LT) B4 and LTC4 in retinal pigment epithelia (RPE) from Xenopus laevis were measured by radioimmunoassay (RIA). RPE were isolated during various stages of photoreceptor renewal to determine possible alterations in 5-lipoxygenase activity concurrent with photoreceptor detachment and phagocytosis. Both LTC4 and LTB4 were released to RPE incubation media, although levels of LTB4 in unstimulated RPE were close to the limits of detection by RIA. Incubation of RPE with the calcium ionophore A23187 increased the levels of both LTB4 and LTC4. When animals were maintained on a cycle of 12 hr light/dark, normal photoreceptor shedding, as measured by histological quantitation of the appearance of phagosomes in the RPE, occurred 1 hr after light onset. Levels of LTC4 in RPE were lower 1 hr after light onset, as compared to 1 hr prior to light onset. Due to the low levels of LTB4, no significant differences could be detected. However, when LTB4 levels were elevated with A23187, LTB4 also declined 1 hr after light onset. When animals were maintained in constant light for 5 days, then exposed to 2 hr dark and 2 hr light, a massive shedding response occurred. Levels of LTC4 were stimulated 5 min after light onset (prior to detectable shedding) and declined below dark levels as shedding progressed. These data suggest a correlation between 5-lipoxygenase activity and the events of photoreceptor shedding and phagocytosis.