scholarly journals Mesoscopic cortical network reorganization during recovery of partial optic nerve injury in GCaMP6s mice

2020 ◽  
Author(s):  
Marianne Groleau ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Matthieu P. Vanni ◽  
Jacqueline L. Higgins ◽  
Anne-Sophie Vézina Bédard ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Optic Nerve ◽  
Nerve Injury ◽  
Cortical Plasticity ◽  
Ganglion Cells ◽  
Wide Field ◽  
Optic Nerve Injury ◽  
Nerve Crush ◽  
Correlated Activity

AbstractAs the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 30 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated at the same time points. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 30 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

scholarly journals Mesoscopic cortical network reorganization during recovery of optic nerve injury in GCaMP6s mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marianne Groleau ◽  
Mojtaba Nazari-Ahangarkolaee ◽  
Matthieu P. Vanni ◽  
Jacqueline L. Higgins ◽  
Anne-Sophie Vézina Bédard ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Optic Nerve ◽  
Nerve Injury ◽  
Cortical Plasticity ◽  
Ganglion Cells ◽  
Wide Field ◽  
Optic Nerve Injury ◽  
Nerve Crush ◽  
Correlated Activity

AbstractAs the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the spontaneous plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 31 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated in parallel. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 31 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

scholarly journals Longitudinal In Vivo Imaging of Retinal Ganglion Cells and Retinal Thickness Changes Following Optic Nerve Injury in Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e40352 ◽  
Author(s):  
Balwantray C. Chauhan ◽  
Kelly T. Stevens ◽  
Julie M. Levesque ◽  
Andrea C. Nuschke ◽  
Glen P. Sharpe ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Injury ◽  
Retinal Ganglion Cells ◽  
In Vivo Imaging ◽  
Ganglion Cells ◽  
Retinal Thickness ◽  
Retinal Ganglion ◽  
Optic Nerve Injury

scholarly journals Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway

2021 ◽  
Vol 23 (1) ◽  
pp. 385
Author(s):  
Jie Chen ◽  
Hui Li ◽  
Changming Yang ◽  
Yinjia He ◽  
Tatsuo Arai ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Injury ◽  
Ganglion Cells ◽  
Crush Injury ◽  
Optic Nerve Crush ◽  
Nerve Crush ◽  
Injury Model ◽  
Nerve Crush Injury

Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.

scholarly journals MEF2 transcription factors differentially contribute to retinal ganglion cell loss after optic nerve injury

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242884
Author(s):  
Xin Xia ◽  
Caroline Y. Yu ◽  
Minjuan Bian ◽  
Catalina B. Sun ◽  
Bogdan Tanasa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Optic Nerve ◽  
Nerve Injury ◽  
Neuroprotective Effect ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Post Translational Modification ◽  
Optic Nerve Injury ◽  
Nerve Crush

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies.

scholarly journals Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury

Drug Delivery ◽  
2020 ◽  
Vol 27 (1) ◽  
pp. 556-564
Author(s):  
Dongmei Wang ◽  
Mengmeng Luo ◽  
Baoshan Huang ◽  
Wa Gao ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Injury ◽  
Ganglion Cells ◽  
Optic Nerve Injury ◽  
Thermosensitive Hydrogel

scholarly journals Dynamic changes in cell size and corresponding cell fate after optic nerve injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin M. Davis ◽  
Li Guo ◽  
Nivedita Ravindran ◽  
Ehtesham Shamsher ◽  
Veerle Baekelandt ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Cell Size ◽  
Nerve Injury ◽  
Cell Fate ◽  
Adaptive Optics ◽  
Retinal Cell ◽  
Multiple Time ◽  
Optic Nerve Injury ◽  
Over Time

AbstractIdentifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.

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