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

被引：0

作者：

Michal Geva

Noga Gershoni-Emek

Luana Naia

Philip Ly

Sandra Mota

Ana Cristina Rego

Michael R. Hayden

Leonard A. Levin

机构：

[1] Prilenia Therapeutics,CNC

[2] University of Coimbra,Center for Neuroscience and Cell Biology

[3] University of British Columbia,The Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute

[4] University of Coimbra,FMUC

[5] McGill University,Faculty of Medicine

[6] McGill University,Department of Ophthalmology and Visual Sciences

[7] McGill University,Department of Neurology and Neurosurgery

[8] Karolinska Institutet,Montreal Neurological Institute

来源：

Scientific Reports | / 11卷

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摘要：

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.

引用

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