scholarly journals Light-evoked activity and BDNF regulate mitochondrial dynamics and mitochondrial localized translation

2018 ◽  
Author(s):  
Alex Kreymerman ◽  
Jessica E. Weinstein ◽  
Sahil H. Shah ◽  
David N. Buickians ◽  
Anne Faust ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Mitochondrial Dynamics ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Axon Development ◽  
Size Number ◽  
Gene And Protein Expression ◽  
Eye Opening ◽  
Evoked Activity

AbstractMitochondria coordinate diverse functions within neurites, including signaling events for axonal maintenance, and degeneration. However, less is known about the role of mitochondria in axon development and maturation. Here we find that in maturing retinal ganglion cells (RGCs) in vivo, axonal mitochondria increase in size, number, and total area throughout development. We demonstrate through multiple approaches in vivo that the mechanism underlying these mitochondrial changes are dependent on eye opening and associated neuronal activity, which can be mimicked by brain derived neurotrophic factor (BDNF). We report downstream gene and protein expression changes consistent with mitochondrial biogenesis and energetics pathways, and present evidence that the associated transcripts are localized and translated at mitochondria within axons in an activity-dependent manner. Together these data support a novel model for mitochondrial-localized translation in support of intra-axonal mitochondrial dynamics and axonal maturation.

Actions of GABAergic ligands on brisk ganglion cells in the cat retina

1992 ◽  
Vol 9 (3-4) ◽  
pp. 415-425 ◽  
Author(s):  
Frank Müller ◽  
Reimund Boos ◽  
Heinz Wässle
Keyword(s):  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Gamma Aminobutyric Acid ◽  
Stimulus Contrast ◽  
Inhibitory Neurotransmitter ◽  
Suppression Effect ◽  
Cat Retina ◽  
Evoked Activity

AbstractGamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. We tested the actions of iontophoretically applied GABAergic ligands on the spontaneous and stimulus-evoked activity of retinal ganglion cells recorded extracellularly in the in vivo cat eye.GABA as well as GABAA receptor agonists inhibited all brisk ganglion cell types. This action was antagonized by bicuculline. Bicuculline on its own increased the activity of ON-ganglion cells but suppressed OFF-ganglion cells. This suppression effect was abolished during the blockade of glycinergic transmission by strychnine.The GABAB receptor agonist baclofen inhibited OFF-ganglion cells whereas the activity of ON-ganglion cells was either increased or decreased depending on the stimulus contrast. The antagonists, phaclofen and 2-hydroxy saclofen, produced opposite effects to baclofen and antagonized its action.The present study demonstrates that both GABAA and GABAB receptors modulate the activity of ON- and OFF-ganglion cells in the cat retina.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

scholarly journals Endothelin 1-induced retinal ganglion cell death is largely mediated by JUN activation

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Olivia J. Marola ◽  
Stephanie B. Syc-Mazurek ◽  
Gareth R. Howell ◽  
Richard T. Libby
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Retinal Vessel ◽  
Vessel Diameter ◽  
Retinal Ganglion ◽  
Retinal Ganglion Cell Death ◽  
Ganglion Cell Death

Abstract Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs), the output neurons of the retina. Multiple lines of evidence show the endothelin (EDN, also known as ET) system is important in glaucomatous neurodegeneration. To date, the molecular mechanisms within RGCs driving EDN-induced RGC death have not been clarified. The pro-apoptotic transcription factor JUN (the canonical target of JNK signaling) and the endoplasmic reticulum stress effector and transcription factor DNA damage inducible transcript 3 (DDIT3, also known as CHOP) have been shown to act downstream of EDN receptors. Previous studies demonstrated that JUN and DDIT3 were important regulators of RGC death after glaucoma-relevant injures. Here, we characterized EDN insult in vivo and investigated the role of JUN and DDIT3 in EDN-induced RGC death. To accomplish this, EDN1 ligand was intravitreally injected into the eyes of wildtype, Six3-cre+Junfl/fl (Jun−/−), Ddit3 null (Ddit3−/−), and Ddit3−/−Jun−/− mice. Intravitreal EDN1 was sufficient to drive RGC death in vivo. EDN1 insult caused JUN activation in RGCs, and deletion of Jun from the neural retina attenuated RGC death after EDN insult. However, deletion of Ddit3 did not confer significant protection to RGCs after EDN1 insult. These results indicate that EDN caused RGC death via a JUN-dependent mechanism. In addition, EDN signaling is known to elicit potent vasoconstriction. JUN signaling was shown to drive neuronal death after ischemic insult. Therefore, the effects of intravitreal EDN1 on retinal vessel diameter and hypoxia were explored. Intravitreal EDN1 caused transient retinal vasoconstriction and regions of RGC and Müller glia hypoxia. Thus, it remains a possibility that EDN elicits a hypoxic insult to RGCs, causing apoptosis via JNK-JUN signaling. The importance of EDN-induced vasoconstriction and hypoxia in causing RGC death after EDN insult and in models of glaucoma requires further investigation.

scholarly journals Spatial receptive field properties of rat retinal ganglion cells

2011 ◽  
Vol 28 (5) ◽  
pp. 403-417 ◽  
Author(s):  
WALTER F. HEINE ◽  
CHRISTOPHER L. PASSAGLIA
Keyword(s):  
Receptive Field ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Cell Types ◽  
Quantitative Information ◽  
Retinal Ganglion ◽  
X And Y Cells ◽  
Y Cells

AbstractThe rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON–OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.

scholarly journals Otx2 Promotes the Survival of Damaged Adult Retinal Ganglion Cells and Protects against Excitotoxic Loss of Visual Acuity In Vivo

2011 ◽  
Vol 31 (14) ◽  
pp. 5495-5503 ◽  
Author(s):  
R. T. Ibad ◽  
J. Rheey ◽  
S. Mrejen ◽  
V. Forster ◽  
S. Picaud ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Loss Of Visual Acuity

Imaging Mouse Retinal Ganglion Cells and Their Loss In Vivo by a Fundus Camera in the Normal and Ischemia-Reperfusion Model

2008 ◽  
Vol 49 (12) ◽  
pp. 5546 ◽  
Author(s):  
Hiroshi Murata ◽  
Makoto Aihara ◽  
Yi-Ning Chen ◽  
Takashi Ota ◽  
Jiro Numaga ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Ischemia Reperfusion ◽  
Retinal Ganglion ◽  
Fundus Camera

scholarly journals Panton-Valentine Leucocidin Proves Direct Neuronal Targeting and Its Early Neuronal and Glial Impacts a Rabbit Retinal Explant Model

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 455 ◽  
Author(s):  
XuanLi Liu ◽  
Michel J Roux ◽  
Serge Picaud ◽  
Daniel Keller ◽  
Arnaud Sauer ◽  
...  
Keyword(s):  
Cell Activation ◽  
Ganglion Cells ◽  
Glial Activation ◽  
Inflammatory Factors ◽  
In Vivo Model ◽  
Suitable Model ◽  
Dependent Manner ◽  
Retinal Explants ◽  
Glial Changes

: Panton-Valentine leukocidin (PVL) retinal intoxication induces glial activation and inflammatory response via the interaction with retinal neurons. In this study, rabbit retinal explant was used as a model to study neuronal and glial consequences of PVL intoxication. Retinal explants were treated with different concentrations of PVL. PVL location and neuronal and glial changes were examined using immunohistochemistry. Some inflammatory factors were quantified using RT-qPCR at 4 and 8 h. These results were compared with those of control explants. PVL co-localized rapidly with retinal ganglion cells and with horizontal cells. PVL induced Müller and microglial cell activation. Retinal structure was altered and some amacrine and microglial cells underwent apoptosis. Glial activation and cell apoptosis increased in a PVL concentration- and time-dependent manner. IL-6 and IL-8 expression increased in PVL-treated explants but less than in control explants, which may indicate that other factors were responsible for glial activation and retinal apoptosis. On retinal explants, PVL co-localized with neuronal cells and induced glial activation together with microglial apoptosis, which confirms previous results observed in in vivo model. Rabbit retinal explant seems to be suitable model to further study the process of PVL leading to glial activation and retinal cells apoptosis.

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