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Eric J Knott, William C Gordon, Nicolas G Bazan; Neuroprotectin D1 is Synthesized during Moderate Light Preconditioning. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2980.
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NPD1, a lipid mediator made on demand is biosynthesized from DHA. This bioactive mediator attenuates CNV, protects neurons during ischemia reperfusion, and RPE cells from oxidative stress. Bright light induces oxidative stress and other homeostatic disruptions that results in photoreceptor degeneration; however a moderate light (preconditioning) stimulus prior to bright light treatment ameliorates photoreceptor cell death. It has been reported that ischemic preconditioning releases DHA and AA, but the lipid/docosanoid signaling during light induced degeneration has yet to be investigated. Thus, the purpose of this study was to determine if DHA was released and the docosanoids 14-HDHA, 17-HDHA, and NPD1 were synthesized during moderate light preconditioning.
Male Sprague Dawley rats (150-175g) Charles River, were acclimated to facilities for 7-14 days (cage light 40-60 lux) followed by stimulation with moderate light (1200 lux) prior to bright light (18kLux) treatment. Photoreceptor survival was analyzed via SD-OCT and outer retinal thickness (photoreceptor/RPE) reported. Retinas were collected -1h, +1, +4, +8, +11h post preconditioning light onset, lipids extracted, and analyzed via LC-ESI /MS/MS.
Rats exposed to bright light displayed a 50% reduction in superior outer retinal thickness, while rats given moderate light prior to bright light treatment presented with an 8% reduction in outer retinal thickness. Retinas of preconditioned rats showed increased DHA release and synthesis of 17 HDHA, 14 HDHA, and NDP1 throughout the day, as compared to controls.
This data suggests that moderate light preconditioning is neuroprotective through DHA release and synthesis of the docosanoid NPD1. This supports the idea that DHA/NPD1 could prevent or attenuate pathological conditions during early stages of retinal degenerative diseases.
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