December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Endogenous Anti-apoptotic Mechanism in Axotomized Retinal Ganglion Cells: the Involvement of Elevated Akt Phosphorylation
Author Affiliations & Notes
  • K-F So
    Anatomy University of Hong Kong Hong Kong Hong Kong Special Administrative Region of China
  • ZH Cheung
    Anatomy University of Hong Kong Hong Kong Hong Kong Special Administrative Region of China
  • FK W Siu
    Rehabilitation Sciences The Hong Kong Polytechnic University Hong Kong Hong Kong Special Administrative Region of China
  • HK Yip
    Anatomy University of Hong Kong Hong Kong Hong Kong Special Administrative Region of China
  • MC P Leung
    Rehabilitation Sciences The Hong Kong Polytechnic University Hong Kong Hong Kong Special Administrative Region of China
  • W Wu
    Anatomy University of Hong Kong Hong Kong Hong Kong Special Administrative Region of China
  • Footnotes
    Commercial Relationships   K. So, None; Z.H. Cheung, None; F.K.W. Siu, None; H.K. Yip, None; M.C.P. Leung, None; W. Wu, None. Grant Identification: Support: Award from HKU
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1992. doi:
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      K-F So, ZH Cheung, FK W Siu, HK Yip, MC P Leung, W Wu; Endogenous Anti-apoptotic Mechanism in Axotomized Retinal Ganglion Cells: the Involvement of Elevated Akt Phosphorylation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1992.

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

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Abstract

Abstract: : Purpose:We have previously shown that axotomy induced an early release of cytochrome c in axotomized retinal ganglion cells (RGCs) at 1 day post-axotomy (dpa). Interestingly, activation of caspase-9, caspase-3 and nuclear fragmentation were not observed in axotomized RGCs until 3 dpa. We hypothesize that endogenous neuroprotective pathways exist to temporarily halt the progress of apoptosis at a site downstream of cytochrome c release. Methods:Unilateral optic nerve transection 1.5 mm from the optic disc was performed on adult hamster. Operated animals were sacrificed at various time-points after axotomy to investigate the levels of phospho-Akt (Ser 473) in axotomized retinas using western blotting. Alternatively, the operated eyes were injected intravitreally with wortmannin, an inhibitor of PI3K, at 0 and 1 dpa. Animals were sacrificed at 2 dpa to examine the effect of wortmannin injections on phospho-Akt levels, caspase-3 and -9 activation and nuclear fragmentation in axotomized retinas. Results:We found that axotomy induced a rapid but transient increase in Akt phosphorylation in axotomized retinas. Akt activation markedly increased as early as 3 hours post-axotomy and returned to control level at 3 dpa, coinciding with the onset of caspase activation and RGC loss. In addition, attenuating the increase in Akt phosphorylation following axotomy by intravitreal injections of wortmannin induced the presence of activated caspase-3 and -9-positive apoptotic cells in the ganglion cell layer. Conclusion:Our data suggest that axotomy resulted in an increase in Akt phosphorylation, which delayed the onset of apoptotic machinery downstream of cytochrome c release by inhibiting the activation of caspase-9 or -3. Akt may hence serve as an endogenous neuroprotective pathway to limit RGC death following axotomy.

Keywords: 323 apoptosis/cell death • 415 ganglion cells • 489 neuroprotection 
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