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H. Imai, P. E. Fort, M. K. Losiewicz, R. S. J. Singh, C. E. N. Reiter, T. W. Gardner; Igf-2 Modulates the Pro-Survival Action of the Insulin Receptor in the Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4916. doi: https://doi.org/.
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To investigate the IGF-2 effect on the pro-survival action of the insulin receptor in the retina.
Differentiated R28 cells were serum-deprived for 6 hours and treated with the PI3K inhibitor LY294002, the PI3K and mTOR inhibitor PI103, the mTOR inhibitor rapamycin, the JNK-1, -2, -3 inhibitor JNK inibitor-II, the MEK-1, -2 inhibitor U0126, or with the P38MAPK inhibitor SB202190, followed by addition of 10nM IGF-2. Caspase-3/7 activity was compared among all conditions. IGF-2 blocking antibody was injected intravitreally in normal male Sprague-Dawley rats and the retinas were extracted one hour later. Western blot and immunoprecipitation were performed to check the intracellular signaling. Data were analyzed by Mann Whitney-U test.
IGF-2 significantly decreased the caspase-3/7 activity compared with the untreated serum-deprived R28 cells (p<0.01). The effect of IGF-2 was significantly reversed by all inhibitors (p<0.01), except rapamycin and SB202190. IGF-2 blocking antibody reduced retinal IR autophosphorylation.
IGF-2 may be involved in the pro-survival action of the insulin receptor pathway in the retina.
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