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Vinicius Vanzan Pimentel Oliveira, Sebastiao Cronemberger, Nassim S Calixto, Adalmir Morterá Dantas; Effect of light-off stimulus and Kynurenic acid on Retinal Spreading Depression . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3616.
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To test if darkness (light-off stimulus) triggers Retinal Spreading Depression (RSD) and if Kynurenic acid (KYNA) might be considered a neuroprotector drug.
Kynurenic acid (KYNA) is an N-methyl-D-aspartate receptor antagonist that blocks one of the OFF-pathways for retinal transduction of light. KYNA could be a potential inhibitor of RSD cortical spreading depression. As described by Leão (1944), Cortical Spreading Depression is a damaging wave of depolarization that propagates through the brain cortex and is related to many diseases such as stroke, migraine with aura and traumatic brain injury. In 1958, Gouras described Retinal Spreading Depression (RSD). RSD is seen on the retina as a milky wave spreading through the retinal tissue causing a negative external cellular media voltage shift. Thus, RSD has a tremendous impact on the neurons’ survival as it increases the energy spent by neurons and also reduces blood supply by vasoconstriction. RSD can cause many eye disorders such as retinal ischemia, glaucoma and retinal degenerations. When the retina is dark-adapted there is an increase in glutamate release.<br /> Firstly, we described a new technique to trigger RSD. White Leghorn chicks’ eyeballs (n=30) were sectioned along the equator. Their posterior half was put in an acrylic chamber; a modified balanced salt solution (BSS), perfused by a peristaltic pump, nourishes the retina. A 1500 lux lamp was positioned over the retina at a distance of 5cm. After stabilization of the system (15min) the light was turned off.<br /> Using a similar set up, we conducted 30 experiments adding KYNA (120μM) to BSS on a RSD model.
Light-off stimulus was sufficient to trigger RSD without mechanical stimulus. We also observed that KYNA had a dose-effect inhibition response over RSD. KYNA concentration as little as 120 μM was able to block RSD at the light-off stimulus and reduced the RSD voltage shift by 27.3%±3.2%. KYNA concentration of 1,2mM also was able to block RSD without mechanical stimulus.
The light-off stimulus might trigger RSD by increasing glutamate concentration on the extracellular media. The addition of KYNA (120 μM) to the extracellular media was able to inhibit RSD, independent of mechanical stimulus. Therefore, KYNA might be considered a neuroprotector drug.
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