scholarly journals Retina-specific loss ofIkbkap/Elp1causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia

2018 ◽  
Vol 11 (7) ◽  
pp. dmm033746 ◽  
Author(s):  
Yumi Ueki ◽  
Veronika Shchepetkina ◽  
Frances Lefcort
Keyword(s):  
Mouse Model ◽  
Mitochondrial Dysfunction ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Familial Dysautonomia ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Specific Loss

scholarly journals Mouse model of ocular hypertension with retinal ganglion cell degeneration

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0208713 ◽  
Author(s):  
Ryo Mukai ◽  
Dong Ho Park ◽  
Yoko Okunuki ◽  
Eiichi Hasegawa ◽  
Garrett Klokman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ganglion Cell ◽  
Ocular Hypertension ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Cell Degeneration

scholarly journals Optimized OPA1 Isoforms 1 and 7 Provide Therapeutic Benefit in Models of Mitochondrial Dysfunction

2020 ◽  
Vol 14 ◽  
Author(s):  
Daniel M. Maloney ◽  
Naomi Chadderton ◽  
Sophia Millington-Ward ◽  
Arpad Palfi ◽  
Ciara Shortall ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Atrophy ◽  
Therapeutic Interventions ◽  
Fibroblast Cells ◽  
Retinal Ganglion ◽  
Cell Degeneration

Optic Atrophy 1 (OPA1) is a mitochondrially targeted GTPase that plays a pivotal role in mitochondrial health, with mutations causing severe mitochondrial dysfunction and typically associated with Dominant Optic Atrophy (DOA), a progressive blinding disease involving retinal ganglion cell loss and optic nerve damage. In the current study, we investigate the use of codon-optimized versions of OPA1 isoform 1 and 7 as potential therapeutic interventions in a range of in vitro and in vivo models of mitochondrial dysfunction. We demonstrate that both isoforms perform equally well in ameliorating mitochondrial dysfunction in OPA1 knockout mouse embryonic fibroblast cells but that OPA1 expression levels require tight regulation for optimal benefit. Of note, we demonstrate for the first time that both OPA1 isoform 1 and 7 can be used independently to protect spatial visual function in a murine model of retinal ganglion cell degeneration caused by mitochondrial dysfunction, as well as providing benefit to mitochondrial bioenergetics in DOA patient derived fibroblast cells. These results highlight the potential value of OPA1-based gene therapy interventions.

XIAP gene therapy effects on retinal ganglion cell structure and function in a mouse model of glaucoma

Gene Therapy ◽  
2021 ◽  
Author(s):  
Shagana Visuvanathan ◽  
Adam N. Baker ◽  
Pamela S. Lagali ◽  
Stuart G. Coupland ◽  
Garfield Miller ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Cell Structure ◽  
Structure And Function ◽  
Retinal Ganglion ◽  
And Function

scholarly journals Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration

2016 ◽  
Vol 143 ◽  
pp. 28-38 ◽  
Author(s):  
Andrew Osborne ◽  
Marina Hopes ◽  
Phillip Wright ◽  
David C. Broadway ◽  
Julie Sanderson
Keyword(s):  
Ganglion Cell ◽  
Experimental Model ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Retinal Cultures

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Geva ◽  
Noga Gershoni-Emek ◽  
Luana Naia ◽  
Philip Ly ◽  
Sandra Mota ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Degeneration ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Sigma 1 Receptor ◽  
Sigma 1

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.

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