Cargando…

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

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 apoptosi...

Descripción completa

Detalles Bibliográficos
Autores principales: Thomas, Chloe N., Bernardo-Colón, Alexandra, Courtie, Ella, Essex, Gareth, Rex, Tonia S., Blanch, Richard J., Ahmed, Zubair
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377143/
https://www.ncbi.nlm.nih.gov/pubmed/34413361
http://dx.doi.org/10.1038/s41598-021-96107-y
_version_ 1783740594311397376
author Thomas, Chloe N.
Bernardo-Colón, Alexandra
Courtie, Ella
Essex, Gareth
Rex, Tonia S.
Blanch, Richard J.
Ahmed, Zubair
author_facet Thomas, Chloe N.
Bernardo-Colón, Alexandra
Courtie, Ella
Essex, Gareth
Rex, Tonia S.
Blanch, Richard J.
Ahmed, Zubair
author_sort Thomas, Chloe N.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8377143
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-83771432021-08-27 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. Ahmed, Zubair Sci Rep Article 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. Nature Publishing Group UK 2021-08-19 /pmc/articles/PMC8377143/ /pubmed/34413361 http://dx.doi.org/10.1038/s41598-021-96107-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Thomas, Chloe N.
Bernardo-Colón, Alexandra
Courtie, Ella
Essex, Gareth
Rex, Tonia S.
Blanch, Richard J.
Ahmed, Zubair
Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title_full Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title_fullStr Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title_full_unstemmed Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title_short Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
title_sort effects of intravitreal injection of sirna against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377143/
https://www.ncbi.nlm.nih.gov/pubmed/34413361
http://dx.doi.org/10.1038/s41598-021-96107-y
work_keys_str_mv AT thomaschloen effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT bernardocolonalexandra effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT courtieella effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT essexgareth effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT rextonias effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT blanchrichardj effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
AT ahmedzubair effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma