Injury to Cone Synapses by Retinal Detachment: Differences from Rod Synapses and Protection by ROCK Inhibition.

Animals Swine Retinal Rod Photoreceptor Cells / physiology Retinal Detachment / drug therapy rho-Associated Kinases Retinal Cone Photoreceptor Cells Synapses
Rho kinase STED microscopy cone cell pedicle photoreceptor pig retinal detachment spherule synapse synaptic ribbons

Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
27 May 2023
Historique:
received: 15 04 2023
revised: 22 05 2023
accepted: 24 05 2023
medline: 12 6 2023
pubmed: 10 6 2023
entrez: 10 6 2023
Statut: epublish

Résumé

Attachment of a detached retina does not always restore vision to pre-injury levels, even if the attachment is anatomically successful. The problem is due in part to long-term damage to photoreceptor synapses. Previously, we reported on damage to rod synapses and synaptic protection using a Rho kinase (ROCK) inhibitor (AR13503) after retinal detachment (RD). This report documents the effects of detachment, reattachment, and protection by ROCK inhibition on cone synapses. Conventional confocal and stimulated emission depletion (STED) microscopy were used for morphological assessment and electroretinograms for functional analysis of an adult pig model of RD. RDs were examined 2 and 4 h after injury or two days later when spontaneous reattachment had occurred. Cone pedicles respond differently than rod spherules. They lose their synaptic ribbons, reduce invaginations, and change their shape. ROCK inhibition protects against these structural abnormalities whether the inhibitor is applied immediately or 2 h after the RD. Functional restoration of the photopic b-wave, indicating cone-bipolar neurotransmission, is also improved with ROCK inhibition. Successful protection of both rod and cone synapses with AR13503 suggests this drug will (1) be a useful adjunct to subretinal administration of gene or stem cell therapies and (2) improve recovery of the injured retina when treatment is delayed.

Identifiants

DOI: 10.3390/cells12111485 PMID: 37296606 PMC: PMC10253016
pubmed: 37296606
pii: cells12111485
doi: 10.3390/cells12111485
pmc: PMC10253016
pii:
doi:

Substances chimiques

rho-Associated Kinases EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : United States Department of Defense
ID : W81XWH1910819
Organisme : National Institute of Health
ID : S10 OD25182
Organisme : Joseph and Marguerite DiSepio Retina Research Fund
ID : NA
Organisme : New Jersey Lions Eye Research Foundation
ID : NA

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Auteurs

Ellen Townes-Anderson (E)

Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.

Éva Halász (É)

Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.

Ilene Sugino (I)

Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA.

Amy L Davidow (AL)

Department of Biostatistics, New York University School of Global Public Health, 708 Broadway, New York, NY 10003, USA.

Laura J Frishman (LJ)

Department of Vision Sciences, College of Optometry, University of Houston, Martin Luther King Blvd, Houston, TX 77204, USA.

Luke Fritzky (L)

Cellular Imaging and Histology Core, Rutgers New Jersey Medical School, 205 South Orange Avenue, Newark, NJ 07103, USA.

Fawad A K Yousufzai (FAK)

Cellular Imaging and Histology Core, Rutgers New Jersey Medical School, 205 South Orange Avenue, Newark, NJ 07103, USA.

Marco Zarbin (M)

Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA.
ORCID: 0000-0002-7811-7132

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Artiodactyla › Suidae › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Cellules › Neurones › Neurones afférents › Cellules réceptrices sensorielles › Cellules photoréceptrices › Cellules photoréceptrices de vertébré › Cellules photoréceptrices en bâtonnet de la rétine › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Décollement de la rétine › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › rho-Associated Kinases › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Cellules › Neurones › Neurones afférents › Cellules réceptrices sensorielles › Cellules photoréceptrices › Cellules photoréceptrices de vertébré › Cellules photoréceptrices en cône de la rétine › Injury to Cone Synapses by Retinal Detachment:...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › Injury to Cone Synapses by Retinal Detachment:...