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A. Dilly, A. Rajala, G. Li, M. Tanito, R. E. Anderson, R. V. Rajala; Localization and Stress-Induced Activation of Retinal Akt Isoforms. Invest. Ophthalmol. Vis. Sci. 2007;48(13):587.
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Survival factors suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase Akt, which then phosphorylates and inactivates components of the apoptotic machinery. In this study, we examined the localization of retinal Akt isoforms and their activation ex vivo in hyperosmotic stress induced with sorbitol and in vivo with light stress.
We used retinal ex vivo organ cultures, Akt2 knockout mice, and in vivo light stress animal model. Immunoprecipitation and immuohistochemistry methods were used to study the interaction and activation of Akt isoforms.
The Akt2 isoform is specifically activated in the retina in response to hyperosmotic or light stress. The phosphoinositide 3-kinase inhibitor LY294002 failed to block the sorbitol-induced Akt activation. Several proteins in the retina were tyrosine phosphorylated in response to hyperosmotic and light stress. One protein was identified as Grb2-associated binder-1 (Gab1).Immunohistochemical analysis revealed the expression of Akt1, Akt2, and Akt3 in rod photoreceptors as well as the light-induced activation of Akt in rod photoreceptor cells. The Akt2 knockout mice have increased susceptibility to bright light-induced retinal degeneration.
Our results are the first to demonstrate the in vivo activation of Akt in the retina undergoing stress, suggesting that Akt may function as a physiological neuroprotective agent against stress-induced retinal degeneration.
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