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I. Ranchon–Cole, C. Cercy, O. Perche, M. Doly; Inhibition of Phosphatidylinositol 3’–Kinase/akt Signalling Does Not Affect Retinal Light–Susceptibility . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4568.
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To investigate the effect of inhibiting the phosphatidylinositol 3’–Kinase (PI3–Kinase)/Akt signalling on photoreceptor susceptibility to light–induced damage.
Wistar rats were raised in dim–cyclic light. Two eyes from a same rat received a different treatment. Eyes were untreated or injected intravitreally with either DMSO2%, PBS1X or the PI3–kinase inhibitor LY294002 (1,6 mM in DMSO2%) and 16 hours later they were either exposed for 24 hours to a white fluorescent light (2200 lux) or unexposed. Dark–adapted ERGs were recorded before injections, immediately (D1) and 15 days (D15) after light exposure. Retinal morphometric analysis consisting in outer nuclear layer (ONL) thickness measurements along the retina, was done at D15. Retinal caspase–9 activity was measured in the retinas 16 hours after intravitreal injection of PBS1X, DMSO2% or LY294002 as well as in untreated.
In untreated–exposed, PBS1X–exposed or LY294002–exposed eyes, there were significant reductions of the ERGs compared to the unexposed ones, at D1 and D15 and these groups were not different from each other. DMSO2%–exposed group had still significant lower ERGs than the unexposed ones but had significant higher ERGs than the other exposed groups. The ONL thickness measurements confirmed the ERGs recordings. Caspase–9 activity is increased 16 hours after LY294002 injections, corresponding to the light–exposure onset but is unchanged in the other injected eyes compared to the untreated ones.
PI3–kinase inhibitor LY294002 had no toxic effect on the normal retina although it activates caspsae–9, an effector protein of apoptosis. In addition, LY294002 had no effect on retinal susceptibility to light–induced degeneration but inhibited the protective effect of DMSO2%. These data suggest that caspase–9 is not sufficient to induce apoptotic pathway in the retina and that PI3Kinase/Akt pathway can be triggered as survival pathway in neuroprotection.
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