scholarly journals Slit2 is essential for correct retinal ganglion cell axon fasciculation and midline crossing in the zebrafish

2020 ◽  
Author(s):  
Camila Davison ◽  
Flavio R. Zolessi
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Amacrine Cells ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Functional Connection ◽  
Optic Nerves

ABSTRACTThe functional connection of the retina with the brain implies the extension of retinal ganglion cells axons through a long and tortuous path. Slit-Robo signaling has been implicated in axon growth and guidance in several steps of this journey. Here, we analyzed in detail the expression pattern of slit2 in zebrafish embryos by whole-mount fluorescent in situ hybridization, to extend previous work on this and other species. Major sites of expression are amacrine cells in the retina from 40 hpf, as well as earlier expression around the future optic nerve, anterior to the optic chiasm, two prominent cell groups in the anterior forebrain and the ventral midline of the caudal brain and spinal cord. To further characterize slit2 function in retinal axon growth and guidance, we generated and phenotypically characterized a null mutant for this gene, using CRISPR-Cas9 technology. Although no evident defects were found on intraretinal axon growth or in the formation of the optic tracts or tectal innervation, we observed very characteristic and robust impairment on axon fasciculation at the optic nerves and chiasm. The optic nerves appeared thicker and defasciculated only in maternal-zygotic mutants, while a very particular unilateral nerve-splitting phenotype was evident at the optic chiasm in a good proportion of both zygotic and maternal-zygotic mutants. Our results support the idea of a channeling role for Slit molecules in retinal ganglion cell axons at the optic nerve level, in addition to a function in the segregation of axons coming from each nerve at the optic chiasm.

The number, morphology, and distribution of retinal ganglion cells and optic axons in the Australian lungfishNeoceratodus forsteri(Krefft 1870)

2006 ◽  
Vol 23 (2) ◽  
pp. 257-273 ◽  
Author(s):  
HELENA J. BAILES ◽  
ANN E.O. TREZISE ◽  
SHAUN P. COLLIN
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Amacrine Cells ◽  
Resolving Power ◽  
Retinal Ganglion ◽  
Retrograde Labelling

Australian lungfishNeoceratodus forsterimay be the closest living relative to the first tetrapods and yet little is known about their retinal ganglion cells. This study reveals that lungfish possess a heterogeneous population of ganglion cells distributed in a horizontal streak across the retinal meridian, which is formed early in development and maintained through to adult stages. The number and complement of both ganglion cells and a population of putative amacrine cells within the ganglion cell layer are examined using retrograde labelling from the optic nerve and transmission electron-microscopic analysis of axons within the optic nerve. At least four types of retinal ganglion cells are present and lie predominantly within a thin ganglion cell layer, although two subpopulations are identified, one within the inner plexiform and the other within the inner nuclear layer. A subpopulation of retinal ganglion cells comprising up to 7% of the total population are significantly larger (>400 μm2) and are characterized as giant or alpha-like cells. Up to 44% of cells within the retinal ganglion cell layer represent a population of presumed amacrine cells. The optic nerve is heavily fasciculated and the proportion of myelinated axons increases with body length from 17% in subadults to 74% in adults. Spatial resolving power, based on ganglion cell spacing, is low (1.6–1.9 cycles deg−1,n= 2) and does not significantly increase with growth. This represents the first detailed study of retinal ganglion cells in sarcopterygian fish, and reveals that, despite variation amongst animal groups, trends in ganglion cell density distribution and characteristics of cell types were defined early in vertebrate evolution.

Retinal ganglion cell death induced by unilateral tectal ablation in Xenopus

1989 ◽  
Vol 2 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Charles Straznicky ◽  
Roger McCart ◽  
Pál Tóth
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Surgical Removal ◽  
Retinal Ganglion ◽  
Retrograde Degeneration ◽  
Optic Axons ◽  
Optic Fibers ◽  
The Right

AbstractThe survival of retinal ganglion cells (GCs) in the left eye was studied on retinal wholemounts from 2–33 weeks after the surgical removal of the right tectum in juvenile Xenopus. Two to five weeks after tectal removal, about 76% of neurons of the retinal ganglion cell (GC) layer showed signs of retrograde degeneration: swelling of their somata and chromatolysis. Neurons that were not affected by the operation were taken to be either displaced amacrine cells (DAs) or GCs not projecting to the tectum. A portion of GCs showing retrograde degeneration became pyknotic and died within the period of 2–16 weeks after operation. Counts of surviving GCs 20–33 weeks after tectal removal amounted to about 55% of the corresponding neuron number in the right intact retina of the same animal. No discernible GC loss was observed in animals where only the optic fibers were cut at their entry point to the tectum indicating that axotomy alone, followed by rapid regrowth to the target, does not adversely influence the survival of GCs. In long-surviving animals, the left optic nerve was exposed to cobaltic-lysine complex and the position of filled optic axons within the brain determined. Optic axons whose tectal target had been removed were seen to cross over to the left intact tectum via the posterior and pretectal commissures. Aberrant projections were detected to the ipsilateral tectum and the diencephalic periventricular grey in addition to an increased projection to the accessory optic nucleus. It is concluded that the removal of the tectum, the main target of optic fiber projection, induces a very substantial GC death. Since only a portion of optic fibers were able to grow to alternative targets, the surviving GCs may have also included those with main projection areas to the diencephalic visual centers.

scholarly journals When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma

2019 ◽  
Author(s):  
James R Tribble ◽  
Eirini Kokkali ◽  
Amin Otmani ◽  
Flavia Plastino ◽  
Emma Lardner ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Animal Models ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Internal Control ◽  
Visual Pathway ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Reactive Microglia ◽  
Contralateral Eye

AbstractPurposeAnimal models show retinal ganglion cell injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant cross-over of retinal ganglion cell axons from the ipsilateral to the contralateral side at the level of the optic chiasm which may confound findings when damage is restricted to one eye. The effect of unilateral glaucoma on neuroinflammatory damage to the contralateral visual pathway has largely been unexplored.MethodsOcular hypertensive glaucoma was induced unilaterally or bilaterally in the rat and retinal ganglion cell neurodegenerative events were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high resolution imaging, and in the retina by flow cytometry and protein arrays.ResultsFollowing ocular hypertensive stress, peripheral monocytes enter the retina, and microglia become reactive. This effect is more marked in animals with bilateral ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres irrespective of whether ocular hypertension was unilateral or bilateral.ConclusionsThese data suggest that caution is warranted when using the contralateral eye as control in unilateral models of glaucoma.Translational RelevanceUse of a contralateral eye as a control may confound discovery of human relevant mechanism and treatments in animal models. We also identify neuroinflammatory protein responses that warrant further investigation as potential disease modifiable targets.

scholarly journals Clinical electrophysiology of the optic nerve and retinal ganglion cells

Eye ◽  
2021 ◽  
Author(s):  
Oliver R. Marmoy ◽  
Suresh Viswanathan
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Cell Function ◽  
Ganglion Cells ◽  
Pattern Electroretinogram ◽  
Photopic Negative Response ◽  
Clinical Electrophysiology ◽  
Retinal Ganglion

AbstractClinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques. In this review, we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma. The disease groups discussed include hereditary, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.

scholarly journals Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction

2020 ◽  
Author(s):  
James R Tribble ◽  
Amin Otmani ◽  
Shanshan Sun ◽  
Sevannah A Ellis ◽  
Gloria Cimaglia ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Neurodegenerative Disease ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Cell Function ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Neuroprotective Therapy

AbstractNicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. Repleting NAD via dietary supplementation of nicotinamide (a precursor to NAD) is effective in preventing retinal ganglion cell neurodegeneration in mouse models. Supporting this, short-term oral nicotinamide treatment in human glaucoma patients provides a recovery of retinal ganglion cell function implying a protection of visual function. Despite this, the mechanism of neuroprotection and full effects of nicotinamide on retinal ganglion cells is unclear. Glaucoma is a complex neurodegenerative disease in which a mix of healthy, stressed, and degenerating retinal ganglion cells co-exist, and in which retinal ganglion cells display compartmentalized degeneration across their visual trajectory. Therefore, we assess the effects of nicotinamide on retinal ganglion cells in normal physiological conditions and across a range of glaucoma relevant insults. We confirm neuroprotection afforded by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We define a small molecular weight metabolome for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption that can be prevented by nicotinamide. Nicotinamide provides these neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term NAM treatment as a neuroprotective therapy for human glaucoma.One Sentence SummaryThe NAD precursor nicotinamide has a potent neuroprotective effect in the retina and optic nerve, targeting neuronal function, metabolism, and mitochondrial function.

scholarly journals Rat Optic Nerve Oligodendrocytes Develop in the Absence of Viable Retinal Ganglion Cell Axons

1999 ◽  
Vol 146 (6) ◽  
pp. 1365-1374 ◽  
Author(s):  
H. Ueda ◽  
J.M. Levine ◽  
R.H. Miller ◽  
B.D. Trapp
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Basic Protein ◽  
Retinal Ganglion ◽  
Optic Nerves ◽  
Temporal And Spatial Patterns ◽  
Longitudinal Orientation ◽  
Temporal And Spatial

Retinal ganglion cell axons and axonal electrical activity have been considered essential for migration, proliferation, and survival of oligodendrocyte lineage cells in the optic nerve. To define axonal requirements during oligodendrogenesis, the developmental appearance of oligodendrocyte progenitors and oligodendrocytes were compared between normal and transected optic nerves. In the absence of viable axons, oligodendrocyte precursors migrated along the length of the nerve and subsequently multiplied and differentiated into myelin basic protein–positive oligodendrocytes at similar densities and with similar temporal and spatial patterns as in control nerves. Since transected optic nerves failed to grow radially, the number of oligodendrocyte lineage cells was reduced compared with control nerves. However, the mitotic indices of progenitors and the percentage of oligodendrocytes undergoing programmed cell death were similar in control and transected optic nerves. Oligodendrocytes lacked their normal longitudinal orientation, developed fewer, shorter processes, and failed to form myelin in the transected nerves. These data indicate that normal densities of oligodendrocytes can develop in the absence of viable retinal ganglion axons, and support the possibility that axons assure their own myelination by regulating the number of myelin internodes formed by individual oligodendrocytes.

The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Growth Cone ◽  
Expression Patterns ◽  
Optic Tract ◽  
Axon Growth ◽  
Proteolytic Processing ◽  
Retinal Ganglion

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

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