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

Abstract 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 S...

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Autores principales:	Michal Geva, Noga Gershoni-Emek, Luana Naia, Philip Ly, Sandra Mota, Ana Cristina Rego, Michael R. Hayden, Leonard A. Levin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca78b753223b4e7397379916ee16da40
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spelling	oai:doaj.org-article:ca78b753223b4e7397379916ee16da402021-11-14T12:20:32ZNeuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma10.1038/s41598-021-01077-w2045-2322https://doaj.org/article/ca78b753223b4e7397379916ee16da402021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01077-whttps://doaj.org/toc/2045-2322Abstract 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.Michal GevaNoga Gershoni-EmekLuana NaiaPhilip LySandra MotaAna Cristina RegoMichael R. HaydenLeonard A. LevinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michal Geva Noga Gershoni-Emek Luana Naia Philip Ly Sandra Mota Ana Cristina Rego Michael R. Hayden Leonard A. Levin Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
description	Abstract 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.
format	article
author	Michal Geva Noga Gershoni-Emek Luana Naia Philip Ly Sandra Mota Ana Cristina Rego Michael R. Hayden Leonard A. Levin
author_facet	Michal Geva Noga Gershoni-Emek Luana Naia Philip Ly Sandra Mota Ana Cristina Rego Michael R. Hayden Leonard A. Levin
author_sort	Michal Geva
title	Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma
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
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca78b753223b4e7397379916ee16da40
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Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma

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