Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma.

Thomas, Chloe N, Bernardo-Colón, Alexandra, Courtie, Ella, Essex, Gareth, Rex, Tonia S, Blanch, Richard J and Ahmed, Zubair (2021) Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma. Scientific reports, 11 (1). p. 16839. ISSN 2045-2322. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Abstract

Ocular repeated air blast injuries occur from low overpressure blast wave exposure, which are often repeated and in quick succession. We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL/6 mice were exposed to repeated blasts of overpressure air (3 × 2 × 15 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2 × 15 psi ("post-blast") or 48 h before the first blast exposure ("pre-blast") and repeated every 7 days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 "post-blast" injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 "pre-blast" injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections "post-blast" caused greater vitreous inflammation, potentiated by siCASP2, with less in "pre-blast" injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WL Nervous system. Neurology
WW Eyes. Ophthalmology
Divisions: Ambulatory Care > Ophthalmology
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 03 Sep 2021 15:38
Last Modified: 03 Sep 2021 15:38
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4606

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