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Eric J Knott, Blake Ashlyn Lemoyne, Nicolas G Bazan; The Significance of 15 Lipoxygenase-1 and Docosanoid Signaling In Retinal Ischemic Preconditioning. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):15.
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© ARVO (1962-2015); The Authors (2016-present)
Docosanoids are lipids biosynthesized from DHA. NPD1, the first identified docosanoid attenuates CNV, protects neurons during ischemia reperfusion, and RPE cells from oxidative stress. Bright light induces oxidative stress and other homeostatic disturbances that results in photoreceptor degeneration; however an ischemic preconditioning stimulus prior to bright light treatment ameliorates photoreceptor cell death. It has been reported that ischemic preconditioning releases DHA and AA in cardiac cells, but the lipid/docosanoid signaling during retinal ischemic preconditioning (rIPC) has yet to be investigated. Therefore, the purpose of this study was to examine the role of docosanoid signaling, specifically NPD1, in rIPC.
Male Sprague-Dawley rats were anesthetized and preconditioned via increasing intraocular pressure (IOP) 120 mm Hg for 5 minutes via hypodermic needle into the anterior chamber 24 hour prior to bright light exposure. In sham-treated and non- preconditioned animals the IOP was maintained at 10 to 15 mm Hg. The opposite eye of each animal served as the non-ischemic control. Lipids were collected post 40 minutes rIPC and post light damage ± rIPC.
Five minutes of ischemic preconditioning protected photoreceptor from subsequent bright light induced degeneration. Ischemic preconditioning alone stimulated 17 HDHA and NPD1 synthesis. Inhibition of 15 LOX-1 reduced the protection bestowed by rIPC while inhibiting the synthesis of 17 HDHA and NPD1. Bright light further increased the synthesis of these molecules but rIPC plus bright light resulted in lower concentrations than bright light alone.
Our results demonstrate that rIPC protects photoreceptors from oxidative stress-induced cell death while generating 17 HDHA and NPD1. This protection is reduced when 15 LOX-1 is inhibited and these metabolites are reduced. Since NPD1 is a potent neuroprotective metabolite, it is possible that protection is potentiated via DHA-derived NPD1 synthesis. Thus, application of NPD1 and other docosanoids could be used as a potential therapeutic approach for the prevention or attenuation of the initiation or early progression of retinal degenerations.
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