April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Caspase-9-Mediates Photoreceptor Apoptosis After Blunt Ocular Trauma
Author Affiliations & Notes
  • Richard J Blanch
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
    Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom
  • Zubair Ahmed
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Nsikan Akpan
    Department of Pathology & Cell Biology, Columbia University, Birmingham, NY
  • David R Snead
    Histopathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
  • Martin Berry
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Carol M Troy
    Department of Pathology & Cell Biology, Columbia University, Birmingham, NY
  • Robert A H Scott
    Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom
    Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom
  • Ann Logan
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships Richard Blanch, None; Zubair Ahmed, None; Nsikan Akpan, None; David Snead, None; Martin Berry, None; Carol Troy, None; Robert A H Scott, None; Ann Logan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4362. doi:
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      Richard J Blanch, Zubair Ahmed, Nsikan Akpan, David R Snead, Martin Berry, Carol M Troy, Robert A H Scott, Ann Logan; Caspase-9-Mediates Photoreceptor Apoptosis After Blunt Ocular Trauma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4362.

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

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Abstract
 
Purpose
 

Commotio retinae (CR) involves photoreceptor outer segment disruption after blunt ocular trauma and occurs in 0.4% of civilian and 19% of military eye injuries. Photoreceptor degeneration permanently reduces vision in 26% of patients with macula involvement. In animal models of CR, photoreceptors die by both necrosis and apoptosis. Apoptotic mechanisms in CR have not been described. We assessed the role of caspase-9 as a mediator of photoreceptor apoptosis in a rat model of CR.

 
Methods
 

Bilateral CR was induced in rats using ballistic ocular trauma. Caspase-9 activity was assessed by immunohistochemistry, western blots and bVAD-fmk active caspase capture. Caspase-9 was inhibited using unilateral intravitreal injection of the highly specific X-linked inhibitor of apoptosis-baculoviral IAP repeat 3 domain (XBIR3) linked to cell transduction peptide Penetratin 1 (Pen1) after ballistic injury compared with control eyes treated with Pen1 injection alone and retinal function assessed by ERG a-wave amplitude and photoreceptor survival by outer nuclear layer (ONL) thickness. n=6-8 rats/analysis

 
Results
 

Cleaved caspase 9 immunolocalised to photoreceptor inner segments and retinal levels of cleaved caspase-9 increased 5 hours after injury (Fig 1A-B), whereas levels of catalytically active full length caspase-9 increased up to 48 hours (Fig 1C-D). Caspase-9 inhibition by intravitreal injection of Pen1-XBIR3 preserved a-wave amplitude and ONL thickness 14 days after ballistic injury compared to control eyes (Fig 2).

 
Conclusions
 

Caspase 9 initiates photoreceptor apoptosis after CR and its inhibition increases photoreceptor survival and function, highlighting a new therapeutic angle in the treatment of ocular trauma.

     
Keywords: 426 apoptosis/cell death • 648 photoreceptors • 742 trauma  
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