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...
Guardado en:
Autores principales: | , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/121a346046be44c38febc68140c3e75e |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:121a346046be44c38febc68140c3e75e |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT evahalasz rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury AT marcoazarbin rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury AT amyldavidow rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury AT laurajfrishman rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury AT petergombkoto rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury AT ellentownesanderson rockinhibitionreducesmorphologicalandfunctionaldamagetorodsynapsesafterretinalinjury |
_version_ |
1718391768434606080 |