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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chloe N. Thomas, Alexandra Bernardo-Colón, Ella Courtie, Gareth Essex, Tonia S. Rex, Richard J. Blanch, Zubair Ahmed
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b1afdd3ed344166bd25ff7af7659085
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5b1afdd3ed344166bd25ff7af7659085
record_format	dspace
spelling	oai:doaj.org-article:5b1afdd3ed344166bd25ff7af76590852021-12-02T18:51:41ZEffects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma10.1038/s41598-021-96107-y2045-2322https://doaj.org/article/5b1afdd3ed344166bd25ff7af76590852021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96107-yhttps://doaj.org/toc/2045-2322Abstract 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.Chloe N. ThomasAlexandra Bernardo-ColónElla CourtieGareth EssexTonia S. RexRichard J. BlanchZubair AhmedNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chloe N. Thomas Alexandra Bernardo-Colón Ella Courtie Gareth Essex Tonia S. Rex Richard J. Blanch Zubair Ahmed Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
description	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.
format	article
author	Chloe N. Thomas Alexandra Bernardo-Colón Ella Courtie Gareth Essex Tonia S. Rex Richard J. Blanch Zubair Ahmed
author_facet	Chloe N. Thomas Alexandra Bernardo-Colón Ella Courtie Gareth Essex Tonia S. Rex Richard J. Blanch Zubair Ahmed
author_sort	Chloe N. Thomas
title	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_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_sort	effects of intravitreal injection of sirna against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b1afdd3ed344166bd25ff7af7659085
work_keys_str_mv	AT chloenthomas effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT alexandrabernardocolon effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT ellacourtie effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT garethessex effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT toniasrex effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT richardjblanch effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma AT zubairahmed effectsofintravitrealinjectionofsirnaagainstcaspase2onretinalandopticnervedegenerationinairblastinducedoculartrauma
_version_	1718377386935844864

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

Ejemplares similares