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J. Wang, S. Chollangi, R. Anderson, J. Ash; Endogenous Neuroprotection Induced by STAT3 Activation Is Independent of Akt or FGF2. Invest. Ophthalmol. Vis. Sci. 2009;50(13):683.
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We have recently shown that the transcription factor STAT3 is activated with chronic stress and that it likely plays an essential role in stress induced protection of retinal photoreceptors possibly through regulating fibroblast growth factor 2 (FGF2) and Akt2 expression. The purpose of this study was to determine if either FGF2 or Akt2 are essential for chronic stress induced protection of photoreceptors.
Albino Balb/C mice were preconditioning to mild oxidative stress by exposing them to cyclic bright light (600lux; 6AM to 6PM for 6 days). WT or Akt2 knockout mice (Akt2-/-) were subjected to severe light stress (4 hours at 4000lux) after preconditioning. Photoreceptor function and survival was measured using electroretinography (ERGs) and histological analysis. Activation of signal transduction and protein expression was measured by Western blots. MRNA was measured by quantitative real-time PCR.
After preconditioning, FGF2 mRNA and protein levels were upregulated. Total Akt levels were unchanged and Akt was not activated by preconditioning. Genetic deletion of Akt2 (Akt2-/- mice) did not diminish preconditioning induced protection from light damage. Surprisingly, FGF2 was not induced by preconditioning in Akt2 knockout mice.
The observation that Akt2-/- mice had normal stress-induced protection without induced FGF2 upregulation, suggests that neither Akt2 nor FGF2 play an essential role in chronic stress-induced protection. This is in contrast to previous studies that have shown that Akt2 plays a role in protection from acute light damage in the absence of chronic stress. We hypothesize that there are two major pathways for photoreceptor protection; one for an acute stress that utilizes Akt2, and another for chronic stress that utilizes STAT3 activation. This would predict that STAT3 may play a more important role in protecting photoreceptors from inherited retinal degenerations.
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