scholarly journals Differential Expression of DSCAM Guides the Patterning of Retinal Axons Along Their Path and at Their Target in the Developing Xenopus Visual System

2021 ◽  
Author(s):  
Rommel Andrew Santos ◽  
Rodrigo Del Rio ◽  
Alexander Delfin Alvarez ◽  
Gabriela Romero ◽  
Brandon Zarate Vo ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Visual System ◽  
Ganglion Cells ◽  
Retinal Axons ◽  
Topographic Organization ◽  
Retinotopic Organization ◽  
Staining Techniques ◽  
Strong Candidate ◽  
Tectal Neurons ◽  
Retinal Fibers

Abstract Background The Xenopus retinotectal circuit is organized topographically, where the dorsal-ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards their target in the tectum, remain unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path.Methods Using a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, followed to the optic nerve into the chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We also assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum. Results Highest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Downregulating DSCAM levels affected the segregation and proper sorting of medial axon fibers, derived from ventral RGCs, within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization. ConclusionThese findings together with the observation that DSCAM immunoreactivity accumulates on the primary dendrites of tectal neurons indicates that DSCAM exerts multiple roles in coordinating retinotopic order and connectivity in the developing vertebrate visual system.

Pathways of regenerated retinotectal axons in goldfish

Development ◽  
1986 ◽  
Vol 93 (1) ◽  
pp. 1-28
Author(s):  
Claudia A. O. Stuermer
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Normal Development ◽  
Ganglion Cells ◽  
Optic Tract ◽  
Spatiotemporal Pattern ◽  
Retinal Ganglion ◽  
Retinal Axons ◽  
Age Related ◽  
Regenerated Fibres

This study investigates the order of regenerating retinal axons in the goldfish. The spatiotemporal pattern of axon regrowth was assessed by applying horseradish peroxidase (HRP) to regenerating axons in the optic tract at various times after optic nerve section and by analysing the distribution of retrogradely labelled ganglion cells in retina. At all regeneration stages labelled ganglion cells were widely distributed over the retina. There was no hint that axons from central (older) ganglion cells might regrow earlier, and peripheral (younger) ganglion cells later, as occurs in normal development. The absence of an age-related ordering in the regenerated optic nerve was demonstrated by labelling a few axon bundles intraorbitally with HRP (Easter, Rusoff & Kish, 1981) caudal to the previous cut. The retrogradely labelled cells in retina were randomly distributed in regenerates andnot clustered in annuli as in normals. Tracing regenerating axons which were stained anterogradelyfrom intraretinal HRP applications or retrogradely from single labelled tectal fascicles illustrated the fact that the regenerating axons coursed in abnormal routes in the optic nerve and tract. On the surface of the tectum regenerated fibres re-established a fascicle fan. The retinal origin of tectal fascicles was assessed by labelling individual peripheral, intermediate and rostral fascicles with HRP. The retrogradely labelled ganglion cells in the retina were often more widely distributed than in normals, but were mostly found in peripheral, intermediate and central retina, respectively. The order of fibre departure from each tectal fascicle was revealed by placing HRP either on the fascicle's proximal or on its distal half. With proximal labelling sites labelled ganglion cells were found in the temporal and nasal retina, and with distal labelling sites labelled ganglion cells were confined to nasal retina only. Further, the axonal trajectories of anterogradely labelled dorsotemporal retinal ganglion cells were compared to those of dorsonasal retinal ganglion cells in tectal whole mounts. Dorsotemporal axons were confined to the rostral tectal half, whereas dorsonasal axons followed fascicular routes into the fascicles' distal end and reached into caudal tectum. This suggests that the fibres exited along their fascicle's course in a temporonasal sequence. Thus in the tectum, fibres in fascicles restore a gross spatial and age-related order and tend to follow their normal temporonasal sequence of exit.

scholarly journals Differential Change in Retina Structure and Function in Children and Adolescents with Drusens of the Optic Nerve Disk

2018 ◽  
Vol 15 (2S) ◽  
pp. 73-81
Author(s):  
A. G. Shchuko ◽  
D. Yu. Samsonov ◽  
S. I. Zhukova ◽  
T. N. Iureva ◽  
I. M. Mikhalevich ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Visual System ◽  
Children And Adolescents ◽  
Ganglion Cells ◽  
Control Group ◽  
Clinical Group ◽  
Ophthalmological Examination ◽  
Functional Changes ◽  
The Third ◽  
And Function

The first histological and clinical description of the optic nerve drusens was given in the 19th century. Then authors considered drusens as congenital pathologies, and a study of 1999 showed that drusen is not the primary pathology, but the dysplasia of the optic nerve disk and its circulation predisposes to the formation of drusen. Central vision in patients with drusens of the optic nerve disc is reduced rarely, and their diagnosis is reduced to ascertaining of the fact of having drusen without taking into account the structural and functional changes in the visual system.Purpose of the work: to identify the pattern of changes in visual functions in children and adolescents with druses of the optic nerve disk, the development and addition of classification criteria.Patients and methods. 45 children with drusens were examined, a comprehensive analysis of the visual system included a standard ophthalmological examination, a comprehensive study of visual system with ultrasound scanning, OCT and OCTA, standard automated and pulsarperimetry.Based on the results of the cluster analysis, a graph of the distribution of patients into three groups (control group and two clinical groups) was constructed, and the structural and functional state of the visual system was analyzed. Drusens in children in the second group we marked as “peripheral”, and in the third — “central”. The carried out researches have shown, that the revealed disturbances are more expressed in the third clinical group. All this determines the need to complement the clinical classification of drusens and their separation depending on the location relative to the vessels of the optic nerve disk to the central and peripheral. The compression effect of drusen is accompanied with changes in the volume of the optic nerve disc, a violation of retinal hemodynamics, damage to the neuroglia and ganglion cells, which allows treating this pathology as a progressive neuroopticopathy, and the revealed dependence of changes on the localization of druses requires supplementing the existing classification. 

A light- and electron-microscopic investigation of the optic tectum of the frog, Rana pipiens, II: The neurons that give rise to the crossed tecto-bulbar pathway

1990 ◽  
Vol 4 (6) ◽  
pp. 519-531 ◽  
Author(s):  
Thomas E. Hughes
Keyword(s):  
Optic Tectum ◽  
Ganglion Cells ◽  
Retrograde Transport ◽  
Microscopic Investigation ◽  
Electron Microscopic Investigation ◽  
Retinal Ganglion ◽  
Electron Microscopic ◽  
Retinal Axons ◽  
Tectal Neurons ◽  
Apical Dendrites

AbstractThe superficial layers of the frog's optic tectum, Potter's (1969) layers A-G, comprise a complex neuropil made up of many afferent axons, the somata of a few neurons, and many dendrites from the neurons located in the deeper layers. Different types of retinal axons are believed to terminate in different layers (Maturana et al., 1960; Kuljis & Karten, 1988; Sargent et al., 1989), but little is known about the relationships between each type of input and the dendrites of the deep tectal neurons that extend into these superficial layers. The present study used the method of retrograde transport of horseradish peroxidase to study the synaptic contacts on the dendrites of the neurons that give rise to the crossed tecto-bulbar pathway. These cells have apical dendrites that ascend through the superficial retino-recipient layers.The somata of the cells that give rise to the crossed tecto-bulbar pathway are located in the superficial half of layer 6, preferentially clustered along the caudal, lateral, and rostral margins of the tectum. The somata of these cells range from 8−30 ¼m in diameter. Their axons are large (2−4 ¼m in diameter) myelinated fibers that arise from either their somata or proximal dendrites. Their axons travel within the deep medullary layer to leave the tectum at the lateral margin. Their dendritic arbors extend obliquely through the superficial layers to reach layer B where they turn and extend within the layer for up to 0.5 mm. The somata of these cells receive only a scant synaptic input. In contrast, their dendrites receive input in every layer, but the nature of this input varies from layer to layer. Synaptic terminals that resemble retinal ganglion cell boutons contact the labeled dendrites in layers B, F, and G. This indicates that the dendrites may receive monosynaptic input from several types of retinal ganglion cells. Terminals with small, flattened vesicles also contact the dendrites of these cells in each layer. In layer F and below, the terminals with flattened vesicles constitute 15% of the contacts; above layer F they constitute only 5−8% of the contacts. Terminals with medium-sized, flattened vesicles also contact the dendrites of these cells in every layer and constitute a large proportion of their input (33−95%). The latter terminals resemble those that are often postsynaptic to retinal terminals.

scholarly journals Inhibition to excitation ratio regulates visual system responses and behavior in vivo

2011 ◽  
Vol 106 (5) ◽  
pp. 2285-2302 ◽  
Author(s):  
Wanhua Shen ◽  
Caroline R. McKeown ◽  
James A. Demas ◽  
Hollis T. Cline
Keyword(s):  
Information Processing ◽  
Optic Nerve ◽  
Synaptic Transmission ◽  
Visual System ◽  
Receptive Fields ◽  
Field Size ◽  
Visually Guided ◽  
Synaptic Inputs ◽  
Tectal Neurons ◽  
Spike Latency

The balance of inhibitory to excitatory (I/E) synaptic inputs is thought to control information processing and behavioral output of the central nervous system. We sought to test the effects of the decreased or increased I/E ratio on visual circuit function and visually guided behavior in Xenopus tadpoles. We selectively decreased inhibitory synaptic transmission in optic tectal neurons by knocking down the γ2 subunit of the GABAA receptors (GABAAR) using antisense morpholino oligonucleotides or by expressing a peptide corresponding to an intracellular loop of the γ2 subunit, called ICL, which interferes with anchoring GABAAR at synapses. Recordings of miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory PSCs (mEPSCs) showed that these treatments decreased the frequency of mIPSCs compared with control tectal neurons without affecting mEPSC frequency, resulting in an ∼50% decrease in the ratio of I/E synaptic input. ICL expression and γ2-subunit knockdown also decreased the ratio of optic nerve-evoked synaptic I/E responses. We recorded visually evoked responses from optic tectal neurons, in which the synaptic I/E ratio was decreased. Decreasing the synaptic I/E ratio in tectal neurons increased the variance of first spike latency in response to full-field visual stimulation, increased recurrent activity in the tectal circuit, enlarged spatial receptive fields, and lengthened the temporal integration window. We used the benzodiazepine, diazepam (DZ), to increase inhibitory synaptic activity. DZ increased optic nerve-evoked inhibitory transmission but did not affect evoked excitatory currents, resulting in an increase in the I/E ratio of ∼30%. Increasing the I/E ratio with DZ decreased the variance of first spike latency, decreased spatial receptive field size, and lengthened temporal receptive fields. Sequential recordings of spikes and excitatory and inhibitory synaptic inputs to the same visual stimuli demonstrated that decreasing or increasing the I/E ratio disrupted input/output relations. We assessed the effect of an altered I/E ratio on a visually guided behavior that requires the optic tectum. Increasing and decreasing I/E in tectal neurons blocked the tectally mediated visual avoidance behavior. Because ICL expression, γ2-subunit knockdown, and DZ did not directly affect excitatory synaptic transmission, we interpret the results of our study as evidence that partially decreasing or increasing the ratio of I/E disrupts several measures of visual system information processing and visually guided behavior in an intact vertebrate.

scholarly journals Reggie-1 and reggie-2, two cell surface proteins expressed by retinal ganglion cells during axon regeneration

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 577-587 ◽  
Author(s):  
T. Schulte ◽  
K.A. Paschke ◽  
U. Laessing ◽  
F. Lottspeich ◽  
C.A. Stuermer
Keyword(s):  
Optic Nerve ◽  
Nerve Injury ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amino Acid Level ◽  
Surface Proteins ◽  
Retinal Ganglion ◽  
Optic Nerve Injury ◽  
Western Blots ◽  
Retinal Axons

Fish--in contrast to mammals--regenerate retinal ganglion cell axons when the optic nerve is severed. Optic nerve injury leads to reexpression of proteins, which typically are first expressed in newly differentiated retinal ganglion cells and axons. Here we identified two new proteins of fish retinal ganglion cells, reggie-1 and reggie-2, with monoclonal antibody M802 and molecular cloning techniques. In normal fish, M802 stained the few retinal axons derived from newborn ganglion cells which in fish are added lifelong to the retinal margin. After optic nerve injury, however, M802 labeled all retinal ganglion cells and retinal axons throughout their path into tectum. Consistent with M802 staining, reggie-1 and reggie-2 mRNAs were present in lesioned retinal ganglion cells, as demonstrated by in situ hybridization, but were not detectable in their normal mature counterparts. In western blots with membrane proteins of the adult goldfish brain, M802 recognizes a 48x10(3) Mr protein band. At the amino acid level, 48x10(3) Mr reggie-1 and reggie-2 are 44% identical, lack transmembrane and membrane anchor domains, but appear membrane associated by ionic interactions. Reggie-1 and reggie-2 are homologous to 35x10(3) Mr ESA (human epidermal surface antigen) but are here identified as neuronal surface proteins, present on newly differentiated ganglion cells at the retinal margin and which are reexpressed in mature ganglion cells upon injury and during axonal regeneration.

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.

scholarly journals Molecular Mechanisms behind Inherited Neurodegeneration of the Optic Nerve

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 496
Author(s):  
Alessandra Maresca ◽  
Valerio Carelli
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Mitochondrial Dynamics ◽  
Unmet Need ◽  
Deep Understanding ◽  
Genetic Landscape ◽  
Innovative Therapies ◽  
Energy Dependent

Inherited neurodegeneration of the optic nerve is a paradigm in neurology, as many forms of isolated or syndromic optic atrophy are encountered in clinical practice. The retinal ganglion cells originate the axons that form the optic nerve. They are particularly vulnerable to mitochondrial dysfunction, as they present a peculiar cellular architecture, with axons that are not myelinated for a long intra-retinal segment, thus, very energy dependent. The genetic landscape of causative mutations and genes greatly enlarged in the last decade, pointing to common pathways. These mostly imply mitochondrial dysfunction, which leads to a similar outcome in terms of neurodegeneration. We here critically review these pathways, which include (1) complex I-related oxidative phosphorylation (OXPHOS) dysfunction, (2) mitochondrial dynamics, and (3) endoplasmic reticulum-mitochondrial inter-organellar crosstalk. These major pathogenic mechanisms are in turn interconnected and represent the target for therapeutic strategies. Thus, their deep understanding is the basis to set and test new effective therapies, an urgent unmet need for these patients. New tools are now available to capture all interlinked mechanistic intricacies for the pathogenesis of optic nerve neurodegeneration, casting hope for innovative therapies to be rapidly transferred into the clinic and effectively cure inherited optic neuropathies.

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