Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma

Detalhes bibliográficos
Autor(a) principal: Geva, Michal
Data de Publicação: 2021
Outros Autores: Gershoni-Emek, Noga, Naia, Luana, Ly, Philip, Mota, Sandra, Rego, Ana Cristina, Hayden, Michael R., Levin, Leonard A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/105457
https://doi.org/10.1038/s41598-021-01077-w
Resumo: Optic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.
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spelling Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucomaAnimalsDisease Models, AnimalDose-Response Relationship, DrugGlaucomaMitochondriaNeuroprotective AgentsPiperidinesRatsReactive Oxygen SpeciesReceptors, sigmaRetinal Ganglion CellsOptic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.Springer Nature2021-11-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105457http://hdl.handle.net/10316/105457https://doi.org/10.1038/s41598-021-01077-weng2045-2322Geva, MichalGershoni-Emek, NogaNaia, LuanaLy, PhilipMota, SandraRego, Ana CristinaHayden, Michael R.Levin, Leonard A.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-01T10:14:56Zoai:estudogeral.uc.pt:10316/105457Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:01.753553Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
title Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
spellingShingle Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
Geva, Michal
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Glaucoma
Mitochondria
Neuroprotective Agents
Piperidines
Rats
Reactive Oxygen Species
Receptors, sigma
Retinal Ganglion Cells
title_short Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
title_full Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
title_fullStr Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
title_full_unstemmed Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
title_sort Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
author Geva, Michal
author_facet Geva, Michal
Gershoni-Emek, Noga
Naia, Luana
Ly, Philip
Mota, Sandra
Rego, Ana Cristina
Hayden, Michael R.
Levin, Leonard A.
author_role author
author2 Gershoni-Emek, Noga
Naia, Luana
Ly, Philip
Mota, Sandra
Rego, Ana Cristina
Hayden, Michael R.
Levin, Leonard A.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Geva, Michal
Gershoni-Emek, Noga
Naia, Luana
Ly, Philip
Mota, Sandra
Rego, Ana Cristina
Hayden, Michael R.
Levin, Leonard A.
dc.subject.por.fl_str_mv Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Glaucoma
Mitochondria
Neuroprotective Agents
Piperidines
Rats
Reactive Oxygen Species
Receptors, sigma
Retinal Ganglion Cells
topic Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Glaucoma
Mitochondria
Neuroprotective Agents
Piperidines
Rats
Reactive Oxygen Species
Receptors, sigma
Retinal Ganglion Cells
description Optic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-09
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/105457
http://hdl.handle.net/10316/105457
https://doi.org/10.1038/s41598-021-01077-w
url http://hdl.handle.net/10316/105457
https://doi.org/10.1038/s41598-021-01077-w
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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