scholarly journals Intravitreal Co-Administration of GDNF and CNTF Confers Synergistic and Long-Lasting Protection against Injury-Induced Cell Death of Retinal Ganglion Cells in Mice

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2082 ◽  
Author(s):  
Simon Dulz ◽  
Mahmoud Bassal ◽  
Kai Flachsbarth ◽  
Kristoffer Riecken ◽  
Boris Fehse ◽  
...  
Keyword(s):  
Stem Cell ◽  
Optic Nerve ◽  
Cell Line ◽  
Retinal Ganglion Cells ◽  
Neural Stem Cell ◽  
Neurotrophic Factor ◽  
Ganglion Cells ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush

We have recently demonstrated that neural stem cell-based intravitreal co-administration of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) confers profound protection to injured retinal ganglion cells (RGCs) in a mouse optic nerve crush model, resulting in the survival of ~38% RGCs two months after the nerve lesion. Here, we analyzed whether this neuroprotective effect is long-lasting and studied the impact of the pronounced RGC rescue on axonal regeneration. To this aim, we co-injected a GDNF- and a CNTF-overexpressing neural stem cell line into the vitreous cavity of adult mice one day after an optic nerve crush and determined the number of surviving RGCs 4, 6 and 8 months after the lesion. Remarkably, we found no significant decrease in the number of surviving RGCs between the successive analysis time points, indicating that the combined administration of GDNF and CNTF conferred lifelong protection to injured RGCs. While the simultaneous administration of GDNF and CNTF stimulated pronounced intraretinal axon growth when compared to retinas treated with either factor alone, numbers of regenerating axons in the distal optic nerve stumps were similar in animals co-treated with both factors and animals treated with CNTF only.

scholarly journals Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells After Optic Nerve Crush in Mice

eNeuro ◽  
2017 ◽  
Vol 4 (1) ◽  
pp. ENEURO.0331-16.2016 ◽  
Author(s):  
Liang Feng ◽  
Zhen Puyang ◽  
Hui Chen ◽  
Peiji Liang ◽  
John B. Troy ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Neurotrophic Factor ◽  
Ganglion Cells ◽  
Brain Derived Neurotrophic Factor ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush

Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush

Neuroscience ◽  
2012 ◽  
Vol 224 ◽  
pp. 282-293 ◽  
Author(s):  
Z.Z. Zhang ◽  
Y.Y. Gong ◽  
Y.H. Shi ◽  
W. Zhang ◽  
X.H. Qin ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Rat Model ◽  
Ganglion Cells ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush

scholarly journals Loss of Rbfox1 Does Not Affect Survival of Retinal Ganglion Cells Injured by Optic Nerve Crush

2021 ◽  
Vol 15 ◽  
Author(s):  
Lei Gu ◽  
Jacky M. Kwong ◽  
Joseph Caprioli ◽  
Natik Piri
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Gene Networks ◽  
Rna Binding ◽  
Ganglion Cells ◽  
Statistical Significance ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Significant Difference

Rbfox1 is a multifunctional RNA binding protein that regulates alternative splicing, transcription, mRNA stability and translation. Its roles in neurogenesis and neuronal functions are well established. Recent studies also implicate Rbfox1 in the regulation of gene networks that support cell survival during stress. We have earlier characterized the expression of Rbfox1 in amacrine and retinal ganglion cells (RGCs) and showed that deletion of Rbfox1 in adult animals results in depth perception deficiency. The current study investigates the effect of Rbfox1 downregulation on survival of RGCs injured by optic nerve crush (ONC). Seven days after ONC, animals sustained severe degeneration of RGC axons in the optic nerve and significant loss of RGC somas. Semi-quantitative grading of optic nerve damage in control + ONC, control + tamoxifen + ONC, and Rbfox1–/– + ONC groups ranged from 4.6 to 4.8 on a scale of 1 (normal; no degenerated axons were noted) to 5 (total degeneration; all axons showed degenerated organelles, axonal content, and myelin sheath), indicating a severe degeneration. Among these three ONC groups, no statistical significance was observed when any two groups were compared. The number of RGC somas were quantitatively analyzed in superior, inferior, nasal and temporal retinal quadrants at 0.5, 1, and 1.5 mm from the center of the optic disc. The average RGC densities (cells/mm2) were: control 6,438 ± 1,203; control + ONC 2,779 ± 573; control + tamoxifen 6,163 ± 861; control + tamoxifen + ONC 2,573 ± 555; Rbfox1–/– 6,437 ± 893; and Rbfox1–/– + ONC 2,537 ± 526. The RGC loss in control + ONC, control + tamoxifen + ONC and Rbfox1–/– + ONC was 57% (P = 1.44954E-42), 58% (P = 1.37543E-57) and 61% (P = 5.552E-59) compared to RGC numbers in the relevant uninjured groups, respectively. No statistically significant difference was observed between any two groups of uninjured animals or between any two ONC groups. Our data indicate that Rbfox1-mediated pathways have no effect on survival of RGCs injured by ONC.

Upregulation of Gem relates to retinal ganglion cells apoptosis after optic nerve crush in adult rats

2014 ◽  
Vol 45 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Fan Xu ◽  
Hui Huang ◽  
Yu Wu ◽  
Lu Lu ◽  
Li Jiang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Adult Rats ◽  
Nerve Crush

Down-regulation of semaphorin 3F in rat retinal ganglion cells in response to optic nerve crush

2016 ◽  
Vol 34 (5) ◽  
pp. 378-384 ◽  
Author(s):  
Ji-Ae Ko ◽  
Akira Minamoto ◽  
Yosuke Sugimoto ◽  
Yoshiaki Kiuchi
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Down Regulation ◽  
Nerve Crush ◽  
Semaphorin 3F
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