May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Igf-2 Modulates the Pro-Survival Action of the Insulin Receptor in the Retina
Author Affiliations & Notes
  • H. Imai
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • P. E. Fort
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • M. K. Losiewicz
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • R. S. J. Singh
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • C. E. N. Reiter
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • T. W. Gardner
    Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
  • Footnotes
    Commercial Relationships  H. Imai, None; P.E. Fort, None; M.K. Losiewicz, None; R.S.J. Singh, None; C.E.N. Reiter, None; T.W. Gardner, None.
  • Footnotes
    Support  Juvenile Diabetes Research Foundation International
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4916. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To investigate the IGF-2 effect on the pro-survival action of the insulin receptor in the retina.

Methods: : 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.

Results: : 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.

Conclusions: : IGF-2 may be involved in the pro-survival action of the insulin receptor pathway in the retina.

Keywords: growth factors/growth factor receptors • cell survival • diabetic retinopathy 
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