scholarly journals miRNA Changes in Retinal Ganglion Cells after Optic Nerve Crush and Glaucomatous Damage

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1564
Author(s):  
Ben Mead ◽  
Alicia Kerr ◽  
Naoki Nakaya ◽  
Stanislav I. Tomarev

The purpose of this study was to characterize the miRNA profile of purified retinal ganglion cells (RGC) from healthy and diseased rat retina. Diseased retina includes those after a traumatic optic nerve crush (ONC), and after ocular hypertension/glaucoma. Rats were separated into four groups: healthy/intact, 7 days after laser-induced ocular hypertension, 2 days after traumatic ONC, and 7 days after ONC. RGC were purified from rat retina using microbeads conjugated to CD90.1/Thy1. RNA were sequenced using Next Generation Sequencing. Over 100 miRNA were identified that were significantly different in diseased retina compared to healthy retina. Considerable differences were seen in the miRNA expression of RGC 7 days after ONC, whereas after 2 days, few changes were seen. The miRNA profiles of RGC 7 days after ONC and 7 days after ocular hypertension were similar, but discrete miRNA differences were still seen. Candidate mRNA showing different levels of expression after retinal injury were manipulated in RGC cultures using mimics/AntagomiRs. Of the five candidate miRNA identified and subsequently tested for therapeutic efficacy, miR-194 inhibitor and miR-664-2 inhibitor elicited significant RGC neuroprotection, whereas miR-181a mimic and miR-181d-5p mimic elicited significant RGC neuritogenesis.

Neuroscience ◽  
2012 ◽  
Vol 224 ◽  
pp. 282-293 ◽  
Author(s):  
Z.Z. Zhang ◽  
Y.Y. Gong ◽  
Y.H. Shi ◽  
W. Zhang ◽  
X.H. Qin ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Lei Gu ◽  
Jacky M. Kwong ◽  
Joseph Caprioli ◽  
Natik Piri

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.


2014 ◽  
Vol 45 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Fan Xu ◽  
Hui Huang ◽  
Yu Wu ◽  
Lu Lu ◽  
Li Jiang ◽  
...  

2016 ◽  
Vol 34 (5) ◽  
pp. 378-384 ◽  
Author(s):  
Ji-Ae Ko ◽  
Akira Minamoto ◽  
Yosuke Sugimoto ◽  
Yoshiaki Kiuchi

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