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

Chloe Thomas, Alexandra Bernardo-Colón, Ella Courtie, Gareth Essex, Tonia S Rex, Richard Blanch, Zubair Ahmed

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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.
Original languageEnglish
Article number16839
Number of pages15
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 19 Aug 2021

Bibliographical note

Funding Information:
This study was supported by Fight for Sight PhD Studentship, Grant Number 1560/1561 (RJB and ZA), DoD W81XWH-15-1-0096 (TSR), DoD W81XWH-17-2-0055 (TSR), NEI R01 EY022349 (TSR), NEI U24 EY029893 (TSR), NEI P30 EY008126 (VVRC), Vanderbilt University Medical Center Cell Imaging Shared Resource core facility (Clinical and Translational Science Award Grant UL1 RR024975 from National Center for Research Resources), Research to Prevent Blindness Unrestricted Funds (VEI), Ret. Maj. General Stephen L. Jones, MD Fund (TSR), Potoscnak Family-CSC Research Fund (TSR), and Ayers Research Fund in Regenerative Visual Neuroscience (TSR).

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • cell death in the nervous system
  • cellular neuroscience
  • molecular neuroscience
  • visual system

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