June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Executioner Caspase Activity and Photoreceptor Apoptosis After Blunt Ocular Trauma
Author Affiliations & Notes
  • Richard J Blanch
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
    Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom
  • Zubair Ahmed
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
  • Adam Morgan Thompson
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
  • Nsikan Akpan
    Department of Pathology & Cell Biology, Columbia University, New York, NY
  • david RJ snead
    Pathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
  • Martin Berry
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
  • Carol Troy
    Department of Pathology & Cell Biology, Columbia University, New York, NY
  • Robert A H Scott
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
    Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom
  • Ann Logan
    Neurobiology Section, University of Birmingham, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships Richard Blanch, None; Zubair Ahmed, None; Adam Thompson, 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 June 2015, Vol.56, 6023. doi:https://doi.org/
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      Richard J Blanch, Zubair Ahmed, Adam Morgan Thompson, Nsikan Akpan, david RJ snead, Martin Berry, Carol Troy, Robert A H Scott, Ann Logan; Executioner Caspase Activity and Photoreceptor Apoptosis After Blunt Ocular Trauma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):6023. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

Blunt ocular trauma causes commotio retinae (CR), a condition in which macular photoreceptor degeneration permanently reduces vision in 26% of patients. After experimental CR in rats, photoreceptors die by both necrosis and apoptosis, initiated by caspase-9.<br /> The executioner caspases in CR have not been described and no treatments to prevent photoreceptor loss are available. Accordingly, we assessed the role of caspases-3, -6 and -7 as mediators of photoreceptor apoptosis in a rat model of CR, to identify a mechanism which might highlight potential therapeutic targets.

 
Methods
 

Bilateral CR was induced in rats using ballistic ocular trauma. Caspase activity was assessed by immunohistochemistry and in western blots. Caspase-6 was inhibited using unilateral intravitreal injection of penetratin (Pen1)-linked caspase-6 dominant negative (C6DN) protein 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 on retinal sections. n=6-8 /analysis.

 
Results
 

Active caspase-3 and -7 were not found. Cleaved caspase-6 immunolocalised to photoreceptor somata and retinal levels of cleaved caspase-6 increased 48 hours after injury (Fig 1A-B). Caspase-6 inhibition by intravitreal Pen1-XBIR3 injection reduced a-wave amplitude but did not affect ONL thickness 14 days after ballistic injury compared to control eyes (Fig 2).

 
Conclusions
 

After experimental CR, caspase-6 was the only executioner caspase activated, but its inhibition did not increase photoreceptor survival or function, suggesting that either classical executioner caspases are not implicated, or that pathways alternative to apoptosis become active when caspase-6 is inhibited.  

 
Fig 1. A-B. On western blots, retinal levels of full length (p33-35) caspase-6 were unchanged, the cleaved (p18) form increased up to 48 hours. (*p=0.009). C-D. Levels of cleaved (p17) and full length (p32) caspase-3 were unchanged. E-F. Cleaved caspase-7 was not detected and full length caspase-7 (P35) was unchanged.
 
Fig 1. A-B. On western blots, retinal levels of full length (p33-35) caspase-6 were unchanged, the cleaved (p18) form increased up to 48 hours. (*p=0.009). C-D. Levels of cleaved (p17) and full length (p32) caspase-3 were unchanged. E-F. Cleaved caspase-7 was not detected and full length caspase-7 (P35) was unchanged.
 
 
Fig 2. A. Caspase-6 inhibition caused a small, but statistically significant reduction in retinal function, an effect that was more apparent at higher stimulus intensities (p<0.001). B. ONL thickness after experimental CR in Pen1-C6DN-treated eyes was unchanged compared to control eyes.
 
Fig 2. A. Caspase-6 inhibition caused a small, but statistically significant reduction in retinal function, an effect that was more apparent at higher stimulus intensities (p<0.001). B. ONL thickness after experimental CR in Pen1-C6DN-treated eyes was unchanged compared to control eyes.

 
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