The Role of Lysophosphatidic Acid Receptor (LPA1) in the Oxygen-Induced Retinal Ganglion Cell Degeneration

2009 ◽  
Vol 50 (3) ◽  
pp. 1290 ◽  
Author(s):  
Chun Yang ◽  
Josiane Lafleur ◽  
Bupe R. Mwaikambo ◽  
Tang Zhu ◽  
Carmen Gagnon ◽  
...  
2016 ◽  
Vol 143 ◽  
pp. 28-38 ◽  
Author(s):  
Andrew Osborne ◽  
Marina Hopes ◽  
Phillip Wright ◽  
David C. Broadway ◽  
Julie Sanderson

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Geva ◽  
Noga Gershoni-Emek ◽  
Luana Naia ◽  
Philip Ly ◽  
Sandra Mota ◽  
...  

AbstractOptic 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.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Myoung Sup Shim ◽  
Yuji Takihara ◽  
Keun-Young Kim ◽  
Takeshi Iwata ◽  
Beatrice Y. J. T. Yue ◽  
...  

Abstract Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K−tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.


2013 ◽  
Vol 127 (5) ◽  
pp. 669-680 ◽  
Author(s):  
Noriko Himori ◽  
Kotaro Yamamoto ◽  
Kazuichi Maruyama ◽  
Morin Ryu ◽  
Keiko Taguchi ◽  
...  

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