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Conference Paper: Endogenous Anti-apoptotic Mechanism in Axotomized Retinal Ganglion Cells: the Involvement of Elevated Akt Phosphorylation

TitleEndogenous Anti-apoptotic Mechanism in Axotomized Retinal Ganglion Cells: the Involvement of Elevated Akt Phosphorylation
Authors
Issue Date2002
PublisherAssociation for Research in Vision and Ophthalmology
Citation
Association for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, FL, 5-10 May 2002. In Investigative Ophthalmology & Visual Science, 2002, v. 43 n. 13, Abstract no. 1992 How to Cite?
AbstractPurpose: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.
Persistent Identifierhttp://hdl.handle.net/10722/95530
ISSN

 

DC FieldValueLanguage
dc.contributor.authorSo, KFen_HK
dc.contributor.authorCheung, ZHYen_HK
dc.contributor.authorSiu, FKWen_HK
dc.contributor.authorYip, HKFen_HK
dc.contributor.authorLeung, MCPen_HK
dc.contributor.authorWu, Wen_HK
dc.date.accessioned2010-09-25T16:05:10Z-
dc.date.available2010-09-25T16:05:10Z-
dc.date.issued2002en_HK
dc.identifier.citationAssociation for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, FL, 5-10 May 2002. In Investigative Ophthalmology & Visual Science, 2002, v. 43 n. 13, Abstract no. 1992en_HK
dc.identifier.issn1552-5783-
dc.identifier.urihttp://hdl.handle.net/10722/95530-
dc.description.abstractPurpose: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.-
dc.languageengen_HK
dc.publisherAssociation for Research in Vision and Ophthalmology-
dc.relation.ispartofInvestigative Ophthalmology & Visual Scienceen_HK
dc.titleEndogenous Anti-apoptotic Mechanism in Axotomized Retinal Ganglion Cells: the Involvement of Elevated Akt Phosphorylationen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailSo, KF: hrmaskf@hkucc.hku.hken_HK
dc.identifier.emailYip, HKF: hkfyip@hku.hken_HK
dc.identifier.emailWu, W: wtwu@hkucc.hku.hken_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.identifier.authorityWu, W=rp00419en_HK
dc.identifier.hkuros74643en_HK
dc.identifier.hkuros141349-

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