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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.
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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.
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.
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).
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.
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