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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)
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.
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
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).
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.
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