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Light-evoked arachidonic acid release in the retina: illuminance/duration dependence and the effects of quinacrine, mellitin and lithium

Light-evoked arachidonic acid release

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Abstract

Arachidonic acid (AA) is the precursor molecule of a variety of cellular lipid mediators that interact with retinal physiology. In this study, we investigated the time- and illuminance-dependence of the release of AA in the rat retina in vitro in control and lithium-pretreated rats. We also studied the effects of the specific phospholipase A2 (PLA2) inhibitor quinacrine and the specific PLA2 stimulator mellitin on the release of AA. Isolated rat retinas were labelled with 3H-AA for 90 min in vitro in darkness and the incorporation of AA into retinal phospholipids was monitored by thin-layer chromatography. The release of 3H-AA in the incubation medium was determined under different illuminance and timing conditions, with the addition of quinacrine and mellitin, and after pretreatment of the animals with lithium. Light exposure of the prelabelled isolated retinas evoked up to a two-fold increase in AA release compared with retinas incubated for the same time in darkness. The AA release was dependent on illuminance time (10000 1x white fluorescent light for 0.25, 2, 5 and 10 min) and illuminance level (0, 100, 1000, 5000, and 10 000 1x for 10 min). Complete rhodopsin bleaching occurred after 2 min at 10 000 1x. Quinacrine significantly suppressed the light-elicited AA release whereas mellitin increased the release of AA in dark-adapted and light-exposed retinas. Lithium pretreatment, which is known to potentiate light-evoked rod outer segment disruptions, significantly augmented the light-evoked AA release. Our results confirm a light-stimulated release of AA in the retina. The effects of quinacrine and mellitin suggest that this release may be mediated via the activation of PLA2. Our observation of a time-and illuminance-dependence of AA release may indicate a finely tuned regulation of PLA2 stimulation. Furthermore, PLA2 activation may contribute to the pathogenesis of retinal light damage. By releasing AA, the stimulation of PLA2 may provide the precursor molecule for potent lipid mediators such as prostaglandins and leukotrienes that might contribute to the light-elicited ROS disruptions observed in our experimental model.

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  1. Department of Ophthalmology, University Hospital Zürich, CH-8091, Zürich, Switzerland

    Hans Jung & Charlotte Remé

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  1. Hans Jung
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  2. Charlotte Remé
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Supported by the Wilhelm-Sander-Stiftung, München, Germany and the Swiss National Science Foundation (31.-30131.90)

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Jung, H., Remé, C. Light-evoked arachidonic acid release in the retina: illuminance/duration dependence and the effects of quinacrine, mellitin and lithium. Graefe's Arch Clin Exp Ophthalmol 232, 167–175 (1994). https://doi.org/10.1007/BF00176787

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  • DOI: https://doi.org/10.1007/BF00176787

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