scholarly journals Independent modes of ganglion cell translocation ensure correct lamination of the zebrafish retina

2016 ◽  
Vol 215 (2) ◽  
pp. 259-275 ◽  
Author(s):  
Jaroslav Icha ◽  
Christiane Kunath ◽  
Mauricio Rocha-Martins ◽  
Caren Norden

The arrangement of neurons into distinct layers is critical for neuronal connectivity and function. During development, most neurons move from their birthplace to the appropriate layer, where they polarize. However, kinetics and modes of many neuronal translocation events still await exploration. In this study, we investigate retinal ganglion cell (RGC) translocation across the embryonic zebrafish retina. After completing their translocation, RGCs establish the most basal retinal layer where they form the optic nerve. Using in toto light sheet microscopy, we show that somal translocation of RGCs is a fast and directed event. It depends on basal process attachment and stabilized microtubules. Interestingly, interference with somal translocation induces a switch to multipolar migration. This multipolar mode is less efficient but still leads to successful RGC layer formation. When both modes are inhibited though, RGCs fail to translocate and induce lamination defects. This indicates that correct RGC translocation is crucial for subsequent retinal lamination.

2016 ◽  
Author(s):  
Jaroslav Icha ◽  
Christiane Grunert ◽  
Mauricio Rocha-Martins ◽  
Caren Norden

AbstractThe arrangement of neurons into distinct layers is critical for neuronal connectivity and function of the nervous system. During development, most neurons move from their birthplace to the appropriate layer, where they polarize. However, kinetics and modes of many neuronal translocation events still await exploration. Here, we investigate ganglion cell (RGC) translocation across the embryonic zebrafish retina. After completing their translocation, RGCs establish the most basal retinal layer where they form the optic nerve. Using in toto light sheet microscopy, we show that somal translocation of RGCs is a fast and directed event. It depends on basal process attachment and stabilized microtubules. Interestingly, interference with somal translocation induces a switch to multipolar migration. This multipolar mode is less efficient but still leads to successful RGC layer formation. When both modes are inhibited, RGCs that fail to translocate induce lamination defects, indicating that correct RGC translocation is crucial for subsequent retinal lamination.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lucia Buccarello ◽  
Jessica Dragotto ◽  
Kambiz Hassanzadeh ◽  
Rita Maccarone ◽  
Massimo Corbo ◽  
...  

AbstractRetinal ganglion cell (RGC) loss is a pathologic feature common to several retinopathies associated to optic nerve damage, leading to visual loss and blindness. Although several scientific efforts have been spent to understand the molecular and cellular changes occurring in retinal degeneration, an effective therapy to counteract the retinal damage is still not available. Here we show that eyeballs, enucleated with the concomitant optic nerve cut (ONC), when kept in PBS for 24 h showed retinal and optic nerve degeneration. Examining retinas and optic nerves at different time points in a temporal window of 24 h, we found a thinning of some retinal layers especially RGC’s layer, observing a powerful RGC loss after 24 h correlated with an apoptotic, MAPKs and degradative pathways dysfunctions. Specifically, we detected a time-dependent increase of Caspase-3, -9 and pro-apoptotic marker levels, associated with a strong reduction of BRN3A and NeuN levels. Importantly, a powerful activation of JNK, c-Jun, and ERK signaling (MAPKs) were observed, correlated with a significant augmented SUMO-1 and UBC9 protein levels. The degradation signaling pathways was also altered, causing a significant decrease of ubiquitination level and an increased LC3B activation. Notably, it was also detected an augmented Tau protein level. Curcumin, a powerful antioxidant natural compound, prevented the alterations of apoptotic cascade, MAPKs, and SUMO-1 pathways and the degradation system, preserving the RGC survival and the retinal layer thickness. This ex vivo retinal degeneration model could be a useful method to study, in a short time window, the effect of neuroprotective tools like curcumin that could represent a potential treatment to contrast retinal cell death.


2020 ◽  
Vol 18 (9) ◽  
pp. 695-704 ◽  
Author(s):  
Bei Liu ◽  
Yu-Jia Liu

Background: Carvedilol, which is considered as a nonselective β-adrenoreceptor blocker, has many pleiotropic activities. It also causes great impact on neuroprotection because of its antioxidant ability, which suggested that carvedilol may be effective in protecting RGCs from increased oxidative stress. Objective: To examine the effects of carvedilol on preventing Retinal Ganglion Cell (RGC) death in a mouse model of Optic Nerve Injury (ONI). Methods: C57BL/6J mice were subjected to Optic Nerve Injury (ONI) model and treated with carvedilol or placebo. Histological and morphometric studies were performed; the RGC number, the amount of neurons in the ganglion cell layer and the thickness of the Inner Retinal Layer (IRL) was quantified. The average thickness of Ganglion Cell Complex (GCC) was determined by the Spectral- Domain OCT (SD-OCT) assay. Immunohistochemistry, western blot and quantitative real-time PCR analysis were also applied. Results: Daily treatment of carvedilol reduced RGC death following ONI, and in vivo retinal imaging revealed that carvedilol can effectively prevent retinal degeneration. The expression of chemokines important for micorglia recruitment was deceased with carvedilol ingestion and the accumulation of retinal microglia is reduced consequently. In addition, the ONI-induced expression of inducible nitric oxide synthase in the retina was inhibited with carvedilol treatment in the retina. We also discovered that carvedilol suppressed ONI-induced activation of Apoptosis Signal-regulating Kinase-1 (ASK1) and p38 Mitogen-Activated Protein Kinase (MAPK) pathway. Conclusion: The results of this study indicate that carvedilol can stimulate neuroprotection and neuroregeneration, and may be useful for treatment of various neurodegenerative diseases.


Gene Therapy ◽  
2021 ◽  
Author(s):  
Shagana Visuvanathan ◽  
Adam N. Baker ◽  
Pamela S. Lagali ◽  
Stuart G. Coupland ◽  
Garfield Miller ◽  
...  

2017 ◽  
Vol 426 (2) ◽  
pp. 360-373 ◽  
Author(s):  
G.B. Whitworth ◽  
B.C. Misaghi ◽  
D.M. Rosenthal ◽  
E.A. Mills ◽  
D.J. Heinen ◽  
...  

2017 ◽  
Vol 162 ◽  
pp. 97-103 ◽  
Author(s):  
Zhen Puyang ◽  
Hai-Qing Gong ◽  
Shi-Gang He ◽  
John B. Troy ◽  
Xiaorong Liu ◽  
...  

2018 ◽  
Vol 59 (3) ◽  
pp. 1562 ◽  
Author(s):  
Min H. Kang ◽  
Mengchen Suo ◽  
Chandrakumar Balaratnasingam ◽  
Paula K. Yu ◽  
William H. Morgan ◽  
...  

2015 ◽  
Vol 56 (10) ◽  
pp. 6095 ◽  
Author(s):  
Francisco M. Nadal-Nicolás ◽  
Paloma Sobrado-Calvo ◽  
Manuel Jiménez-López ◽  
Manuel Vidal-Sanz ◽  
Marta Agudo-Barriuso

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