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

被引：9
|
作者：
Geva, Michal [1 ]
Gershoni-Emek, Noga [1 ]
Naia, Luana [2 ,8 ]
Ly, Philip [3 ]
Mota, Sandra [2 ]
Rego, Ana Cristina [2 ,4 ]
Hayden, Michael R. [1 ,3 ]
Levin, Leonard A. [5 ,6 ,7 ]
机构：
[1] Prilenia Therapeut, Herzliyya, Israel
[2] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal
[3] Univ British Columbia, BC Childrens Hosp, Ctr Mol Med & Therapeut, Res Inst, Vancouver, BC, Canada
[4] Univ Coimbra, FMUC Fac Med, Coimbra, Portugal
[5] McGill Univ, Dept Ophthalmol & Visual Sci, Montreal, PQ, Canada
[6] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
[7] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
[8] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
来源：
SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期
关键词：
MITOCHONDRIAL-FUNCTION; NEUROTROPHIC FACTOR; OXIDATIVE STRESS; MURINE MODEL; RGC-5; CELLS; MOUSE MODEL; DEATH; DYSFUNCTION; EXPRESSION; (+)-PENTAZOCINE;
D O I：
10.1038/s41598-021-01077-w
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
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.
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页数：16
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