ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury

Abstract Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage...

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Autores principales:	Éva Halász, Marco A. Zarbin, Amy L. Davidow, Laura J. Frishman, Peter Gombkoto, Ellen Townes-Anderson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/121a346046be44c38febc68140c3e75e
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spelling	oai:doaj.org-article:121a346046be44c38febc68140c3e75e2021-12-02T14:12:41ZROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury10.1038/s41598-020-80267-42045-2322https://doaj.org/article/121a346046be44c38febc68140c3e75e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80267-4https://doaj.org/toc/2045-2322Abstract Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1–2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.Éva HalászMarco A. ZarbinAmy L. DavidowLaura J. FrishmanPeter GombkotoEllen Townes-AndersonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Éva Halász Marco A. Zarbin Amy L. Davidow Laura J. Frishman Peter Gombkoto Ellen Townes-Anderson ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
description	Abstract Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1–2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.
format	article
author	Éva Halász Marco A. Zarbin Amy L. Davidow Laura J. Frishman Peter Gombkoto Ellen Townes-Anderson
author_facet	Éva Halász Marco A. Zarbin Amy L. Davidow Laura J. Frishman Peter Gombkoto Ellen Townes-Anderson
author_sort	Éva Halász
title	ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
title_short	ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
title_full	ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
title_fullStr	ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
title_full_unstemmed	ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
title_sort	rock inhibition reduces morphological and functional damage to rod synapses after retinal injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/121a346046be44c38febc68140c3e75e
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ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury

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