File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: Endogenous Neuroprotective Mechanism of Retinal Ganglion Cells following Transection of the Optic Nerve

TitleEndogenous Neuroprotective Mechanism of Retinal Ganglion Cells following Transection of the Optic Nerve
Authors
Issue Date2002
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSG
Citation
Croucher Advanced Study Institute (ASI) on Molecular Neuroscience, Hong Kong, 6-11 January 2002. In Neurosignals, 2002, v. 11 n. 3, p. 161-162, abstract no. 7 How to Cite?
AbstractOptic nerve transection has been shown to induce retinal ganglion cell (RGC) death mediated by caspase-3 and -9 activation. In this study, we examined the possible role of cytochrome c release in axotomized RGC death. Axotomized RGCs are proposed to die via apoptosis. Caspase-3 activation after axotomy has been shown, and caspase-3 inhibitors or Bcl-2 over-expression has been observed to enhance RGC survival. These studies suggest that caspase-3 may participate in the loss of axotomized RGCs. One of the upstream initiators of the apoptotic pathway is cytochrome c release from the intermembrane space of mitochondria. Released cytochrome c binds to Apaf-1 and activates caspase-9. Activated caspase-9 in turn activates caspase-3. To examine the involvement of the cytochrome c pathway in the apoptosis of axotomized RGCs, the release of cytochrome c post-axotomy was analyzed using immunohistochemistry. At 1, 2, 3, 5, 7, 10 and 14 days post-axotomy (dpa), animals were sacrificed and their eyeballs sectioned. Ten-micrometer retinal sections where the RGCs were prelabeled with retrograde transport of fluoro-Gold were used. The sections were counter-stained with DAPI to reveal nuclear morphology. We found that by 1 dpa, there was a significant increase in cytochrome c immunoreactivity compared to normal, undamaged retinas. The increase peaked at 3 dpa, and declined thereafter. By 10 dpa, cytochrome c immunoreactivity has returned to control level. Based on the findings from other apoptosis studies, this upregulation of cytochrome c immunoreactivity may contribute to axotomized RGC death. Interestingly, all the RGCs that were stained positive for cytochrome c exhibited normal nuclear morphology. Immunohistochemical staining of activated caspase-3 revealed that no caspase-3 activation was observed until 3 dpa. This suggests that cytochrome c release may act upstream of caspase-3 activation and precede any visible nuclear changes. Double immunohistochemical analysis for cytochrome c and activated caspase-3 showed that the two staining exhibit no co-localization. The lack of co-localization and the lag between the onset of cytochrome c and activated caspase- 3 staining suggests that there is a temporal gap between the two events. To examine the mechanism underlying the apparent temporal gap between cytochrome c release and caspase activation, the effect of axotomy on Akt activation was investigated. We found that axotomy induced a rapid increase in Akt phosphorylation at 3 h postaxotomy. Phospho-Akt content returned to control level at 3 dpa, coinciding with the onset of caspase activation and RGC loss. Our data suggest that this transient increase may contribute to the delayed activation of caspase-3/9 in axotomized retinas. Attenuating the increase in Akt phosphorylation following axotomy by intravitreal injections of wortmannin, a PI3K inhibitor, resulted in the presence of activated caspase-3 and -9-positive apoptotic cells in the ganglion cell layer. The activation of PI3K/Akt pathway following axotomy may serve as an endogenous protective machinery to counteract the death signals initiated by axotomy.
Persistent Identifierhttp://hdl.handle.net/10722/95415
ISSN
2015 Impact Factor: 1.593
2015 SCImago Journal Rankings: 0.763

 

DC FieldValueLanguage
dc.contributor.authorCheung, ZHYen_HK
dc.contributor.authorSiu, FKWen_HK
dc.contributor.authorYip, HKFen_HK
dc.contributor.authorWu, Wen_HK
dc.contributor.authorLeung, MCPen_HK
dc.contributor.authorSo, KFen_HK
dc.date.accessioned2010-09-25T16:01:33Z-
dc.date.available2010-09-25T16:01:33Z-
dc.date.issued2002en_HK
dc.identifier.citationCroucher Advanced Study Institute (ASI) on Molecular Neuroscience, Hong Kong, 6-11 January 2002. In Neurosignals, 2002, v. 11 n. 3, p. 161-162, abstract no. 7en_HK
dc.identifier.issn1424-862Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/95415-
dc.description.abstractOptic nerve transection has been shown to induce retinal ganglion cell (RGC) death mediated by caspase-3 and -9 activation. In this study, we examined the possible role of cytochrome c release in axotomized RGC death. Axotomized RGCs are proposed to die via apoptosis. Caspase-3 activation after axotomy has been shown, and caspase-3 inhibitors or Bcl-2 over-expression has been observed to enhance RGC survival. These studies suggest that caspase-3 may participate in the loss of axotomized RGCs. One of the upstream initiators of the apoptotic pathway is cytochrome c release from the intermembrane space of mitochondria. Released cytochrome c binds to Apaf-1 and activates caspase-9. Activated caspase-9 in turn activates caspase-3. To examine the involvement of the cytochrome c pathway in the apoptosis of axotomized RGCs, the release of cytochrome c post-axotomy was analyzed using immunohistochemistry. At 1, 2, 3, 5, 7, 10 and 14 days post-axotomy (dpa), animals were sacrificed and their eyeballs sectioned. Ten-micrometer retinal sections where the RGCs were prelabeled with retrograde transport of fluoro-Gold were used. The sections were counter-stained with DAPI to reveal nuclear morphology. We found that by 1 dpa, there was a significant increase in cytochrome c immunoreactivity compared to normal, undamaged retinas. The increase peaked at 3 dpa, and declined thereafter. By 10 dpa, cytochrome c immunoreactivity has returned to control level. Based on the findings from other apoptosis studies, this upregulation of cytochrome c immunoreactivity may contribute to axotomized RGC death. Interestingly, all the RGCs that were stained positive for cytochrome c exhibited normal nuclear morphology. Immunohistochemical staining of activated caspase-3 revealed that no caspase-3 activation was observed until 3 dpa. This suggests that cytochrome c release may act upstream of caspase-3 activation and precede any visible nuclear changes. Double immunohistochemical analysis for cytochrome c and activated caspase-3 showed that the two staining exhibit no co-localization. The lack of co-localization and the lag between the onset of cytochrome c and activated caspase- 3 staining suggests that there is a temporal gap between the two events. To examine the mechanism underlying the apparent temporal gap between cytochrome c release and caspase activation, the effect of axotomy on Akt activation was investigated. We found that axotomy induced a rapid increase in Akt phosphorylation at 3 h postaxotomy. Phospho-Akt content returned to control level at 3 dpa, coinciding with the onset of caspase activation and RGC loss. Our data suggest that this transient increase may contribute to the delayed activation of caspase-3/9 in axotomized retinas. Attenuating the increase in Akt phosphorylation following axotomy by intravitreal injections of wortmannin, a PI3K inhibitor, resulted in the presence of activated caspase-3 and -9-positive apoptotic cells in the ganglion cell layer. The activation of PI3K/Akt pathway following axotomy may serve as an endogenous protective machinery to counteract the death signals initiated by axotomy.-
dc.languageengen_HK
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSGen_HK
dc.relation.ispartofNeurosignalsen_HK
dc.rightsNeurosignals. Copyright © S Karger AG.en_HK
dc.titleEndogenous Neuroprotective Mechanism of Retinal Ganglion Cells following Transection of the Optic Nerveen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1424-862X&volume=11&spage=161&epage=&date=2002&atitle=Endogenous+neuroprotective+mechanism+of+retinal+ganglion+cells+following+transaction+of+the+optic+nerveen_HK
dc.identifier.emailYip, HKF: hkfyip@hku.hken_HK
dc.identifier.emailWu, W: wtwu@hkucc.hku.hken_HK
dc.identifier.emailSo, KF: hrmaskf@hkucc.hku.hken_HK
dc.identifier.authorityWu, W=rp00419en_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1159/000065057-
dc.identifier.hkuros74652en_HK
dc.identifier.hkuros95213-
dc.identifier.hkuros109221-
dc.identifier.volume11en_HK
dc.identifier.spage161en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats