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Loss of protein tyrosine phosphatase 1B increases IGF-I receptor tyrosine phosphorylation but does not rescue retinal defects in IRS2-deficient mice

AuthorsValverde, Ángela M.; Revuelta-Cervantes, Jesús; González-Rodríguez, Águeda; Pardo, Virginia; Burks, Deborah J.; Arroba, Ana I.
Issue Date2013
Citation23RD EASDec Meeting (2013)
Abstract[Introduction]: This study was designed to evaluate role of protein tyrosine phosphatase 1B in mediating IGF-IR/Akt signaling cascade in the retina. [Purpose]: Our goal was to analyze IGF-IR-ediated survival signaling and visual function in PTP1B-deficient (PTP1B-/-) mice and double mutant mice deficient in both PTP1B and IRS2 (IRS2-/-/PTP1B-/-) in comparison to wild-type and IRS2-deficient (IRS2-/-) mice. [Methods]: IGF-IR tyrosine phosphorylation and Akt serine 473 phosphorylation were analyzed by western blot in organotypic retinal explants stimulated with IGF-I. Immunohistochemistry was used to evaluate retinal structure preservation in mice at 9 weeks. Visual function was evaluated by Electroretinographic (ERG) recording in mice at 5 and 9 weeks. [Results]: IGF-IR tyrosine phosphorylation and Akt serine phosphorylation increased in retinal explants of wild-type mice stimulated with IGF-I in a dose-dependent manner. In PTP1B-/- retinal explants, these responses were enhanced. Conversely, in retinas from IRS2-/- mice levels of PTP1B were increased and IGF-IR-mediated Akt phosphorylation decreased as compared to the wild-type control. PTP1B deletion in IRS2-/- mice also enhanced IGF-IR tyrosine phosphorylation but, unexpectedly, the response to IGF-I in Akt phosphorylation remained decreased as observed in IRS2-/- mice. PTEN was increased in IRS2-/- retinas and remained elevated in IRS2-/-/PTP1B-/- mice. Histological evaluation revealed alterations in various structures of the retina in both IRS2-/- and IRS2-/-/PTP1B-/- mice, specifically in the outer nuclear layer (ONL) and retinal outer segments (ROS). ERG analysis revealed that PTP1B deficiency did not restore normal visual function in IRS2-/- mice. [Conclusions]: Although PTP1B deficiency increased IGF-IR tyrosine phosphorylation in retinal explants of IRS2-/- mice, it was unable to restore Akt phosphorylation probably due to elevated PTEN levels. Consequently, structural and functional visual defects of IRS2-/- mice were not improved.
DescriptionResumen del trabajo presentado al 23rd Meeting of the European Association for the Study of Diabetes Eye Complications Study Group (EASDec), celebrado en Barcelona (España) del 23 al 25 de mayo de 2013.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
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