Regeneration of dopaminergic neurons in goldfish retina

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 913-919 ◽  
Author(s):  
J.E. Braisted ◽  
P.A. Raymond
Keyword(s):  
Dopaminergic Neurons ◽  
Developmental Process ◽  
Ganglion Cells ◽  
Outer Nuclear Layer ◽  
Cell Loss ◽  
Cell Types ◽  
High Dose ◽  
Double Labeling ◽  
6 Hydroxydopamine ◽  
Goldfish Retina

The conditions necessary to trigger regeneration of dopaminergic neurons were investigated in the goldfish retina. Intraocular injection of 6-hydroxydopamine (6-OHDA) was used to destroy dopaminergic neurons, and neuronal regeneration was monitored by injections of the thymidine analog bromodeoxyuridine (BUdR). Regenerated dopaminergic neurons, (identified by double-labeling with anti-tyrosine hydroxylase and anti-BUdR antibodies) were found within 3 weeks after 2 injections of 0.6 mg/ml 6-OHDA (estimated intraocular concentration), but not after injection of lower doses. All retinas with regenerated dopaminergic neurons also contained other types of regenerated neurons, including cones and ganglion cells, consistent with nuclear counts which revealed non-selective cell loss (34–36%) in both the outer and inner nuclear layers after exposure to the high dose, but not lower doses of 6-OHDA. Regenerated neurons were produced by clusters of dividing neuroepithelial cells probably derived from rod precursors in the outer nuclear layer. These results demonstrate that dopaminergic neurons will not regenerate after they are selectively ablated but only as part of a developmental process that involves generation of multiple cell types.

Selective regeneration of photoreceptors in goldfish retina

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2409-2419 ◽  
Author(s):  
J.E. Braisted ◽  
T.F. Essman ◽  
P.A. Raymond
Keyword(s):  
Dopaminergic Neurons ◽  
Argon Laser ◽  
Cell Loss ◽  
Specific Class ◽  
Neuronal Progenitors ◽  
Neuroepithelial Cells ◽  
Neuronal Types ◽  
6 Hydroxydopamine ◽  
Goldfish Retina ◽  
Selective Regeneration

Previous work has shown that the neural retina in adult goldfish can regenerate. Following retinal damage elicited by surgical or cytotoxic lesions, missing neurons are replaced by foci of proliferating neuroepithelial cells, which previous studies have suggested are derived from rod precursors. In the intact retina, rod precursors proliferate but produce only new rods. The regenerative responses observed previously have involved replacement of neurons in all retinal layers; selective regeneration of specific neuronal types (except for rod photoreceptors) has not been reported. In the experiments described here, we specifically destroyed either cones alone or cones and rods with an argon laser, and we found that both types of photoreceptors regenerated within a few weeks. The amount of cone regeneration varied in proportion to the degree of rod loss. This is the first demonstration of selective regeneration of a specific class of neuron (i.e., cones) in a region of central nervous tissue where developmental production of that class of neuron has ceased. Selective regeneration may be limited to photoreceptors, however, because when dopaminergic neurons in the inner retina were ablated with intraocular injections of 6-hydroxydopamine, in combination with laser lesions that destroyed photoreceptors, the dopaminergic neurons did not regenerate, but the photoreceptors did. These data support previous studies which showed that substantial cell loss is required to trigger regeneration of inner retinal neurons, including dopaminergic neurons. New observations here bring into question the presumption that rod precursors are the only source of neuronal progenitors during the regenerative response. Finally, a model is presented which suggests a possible mechanism for regulating the phenotypic fate of retinal progenitor cells during retinal regeneration.

Degeneration and Regrowth of Adrenergic Nerve Fibers in the Rat Peripheral Tissues after 6-Hydroxydopamine

1971 ◽  
Vol 49 (4) ◽  
pp. 345-355 ◽  
Author(s):  
J. de Champlain
Keyword(s):  
Ganglion Cells ◽  
Adrenergic Innervation ◽  
Nerve Fibers ◽  
Adrenergic Nerve ◽  
High Dose ◽  
Rat Tissues ◽  
Peripheral Tissues ◽  
Endogenous Noradrenaline ◽  
6 Hydroxydopamine ◽  
Noradrenaline Levels

Histofluorescent and biochemical changes in the adrenergic nervous system were followed up in rat tissues after one single intravenous injection of a high dose of 100 mg/kg of 6-hydroxydopamine (6-OH-DA). This treatment results in the rapid disappearance of terminal and preterminal fibers in the iris, atria, and small arteries of rats, whereas endogenous noradrenaline pools of the heart are 95% depleted. The capacity of the adrenergic nerve to take up and accumulate tritiated noradrenaline is reduced proportionally to the reduction in endogenous noradrenaline levels. These changes are compatible with the concept of a complete sympathectomy induced by the specific toxic action of 6-OH-DA on the adrenergic fibers. This sympathectomy is not permanent, however, and numerous bundles of preterminal fibers start to grow in the iris and atria within 4 to 5 days following injection. Progressively, in the following weeks, these fibers distribute over the whole organ and give birth to terminal fibers which form a new adrenergic plexus in these tissues. A completely normal innervation is restored 2 to 3 months after administration of 6-OH-DA. The endogenous noradrenaline levels rise progressively in parallel to the development of the new plexus of fibers. Since a complete regeneration of the adrenergic innervation can be demonstrated in the weeks following injection of 6-OH-DA, it appears that this compound can selectively destroy the adrenergic terminal and preterminal fibers without causing a degeneration of the adrenergic ganglion cells.

Immuocytochemical analysis of spatial organization of photoreceptors and amacrine and ganglion cells in the tiger salamander retina

2004 ◽  
Vol 21 (2) ◽  
pp. 157-166 ◽  
Author(s):  
JIAN ZHANG ◽  
ZHUO YANG ◽  
SAMUEL M. WU
Keyword(s):  
Ganglion Cell ◽  
Spatial Organization ◽  
Ganglion Cells ◽  
Electrophysiological Study ◽  
Outer Nuclear Layer ◽  
Amacrine Cells ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Proximal Region ◽  
Dorsal Retina

In the present study, using double- or triple-label immunocytochemistry in conjunction with confocal microscopy, we aimed to examine the population and distribution of photoreceptors, GABAergic and glycinergic amacrine cells, and ganglion cells, which are basic but important parameters for studying the structure–function relationship of the salamander retina. We found that the outer nuclear layer (ONL) contained 82,019 ± 3203 photoreceptors, of which 52% were rods and 48% were cones. The density of photoreceptors peaked at ∼8000 cells/mm2 in the ventral and dropped to ∼4000 cells/mm2 in the dorsal retina. In addition, the rod/cone ratio was less than 1 in the central retina but larger than 1 in the periphery. Moreover, in the proximal region of the inner nuclear layer (INL3), the total number of cells was 50,576 ± 8400. GABAergic and glycinergic amacrine cells made up approximately 78% of all cells in this layer, including 43% GABAergic, 32% glycinergic, and 3% GABA/glycine colocalized amacrine cells. The density of these amacrine cells was ∼6500 cells/mm2 in the ventral and ∼3200 cells/mm2 in the dorsal area. The ratio of GABAergic to glycinergic amacrine cells was larger than 1. Furthermore, in the ganglion cell layer (GCL), among a total of 36,007 ± 2010 cells, ganglion cells accounted for 65.7 ± 1.5% of the total cells, whereas displaced GABAergic and glycinergic amacrine cells comprised about 4% of the cells in this layer. The ganglion cell density was ∼1800 cells/mm2 in the ventral and ∼600 cells/mm2 in the dorsal retina. Our data demonstrate that all three major cell types are not uniformly distributed across the salamander retina. Instead, they exhibit a higher density in the ventral than in the dorsal retina and their spatial arrangement is associated with the retinal topography. These findings provide a basic anatomical reference for the electrophysiological study of this species.

scholarly journals β-Cells Different Vulnerability to the Parkinsonian Neurotoxins Rotenone, 1-Methyl-4-phenylpyridinium (MPP+) and 6-Hydroxydopamine (6-OHDA)

2021 ◽  
Vol 14 (8) ◽  
pp. 767
Author(s):  
Marco Carli ◽  
Francesca Vaglini ◽  
Eleonora Risaliti ◽  
Gianluca Citi ◽  
Matilde Masini ◽  
...  
Keyword(s):  
Cell Lines ◽  
Dopaminergic Neurons ◽  
Cell Types ◽  
Population Based ◽  
Β Cells ◽  
Pharmacological Agents ◽  
Develop Type ◽  
6 Hydroxydopamine ◽  
Nanomolar Range

Neurotoxins such as rotenone, 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) are well known for their high toxicity on dopaminergic neurons and are associated with Parkinson’s disease (PD) in murine models and humans. In addition, PD patients often have glucose intolerance and may develop type 2 diabetes (T2D), whereas T2D patients have higher risk of PD compared to general population. Based on these premises, we evaluated the toxicity of these three toxins on pancreatic β-cell lines (INS-1 832/13 and MIN6) and we showed that rotenone is the most potent for reducing β-cells viability and altering mitochondrial structure and bioenergetics in the low nanomolar range, similar to that found in dopaminergic cell lines. MPP+ and 6-OHDA show similar effects but at higher concentration. Importantly, rotenone-induced toxicity was counteracted by α-tocopherol and partially by metformin, which are endowed with strong antioxidative and cytoprotective properties. These data show similarities between dopaminergic neurons and β-cells in terms of vulnerability to toxins and pharmacological agents capable to protect both cell types.

scholarly journals NADPH Oxidase and the Degeneration of Dopaminergic Neurons in Parkinsonian Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Marina S. Hernandes ◽  
Cecília C. Café-Mendes ◽  
Luiz R. G. Britto
Keyword(s):  
Nadph Oxidase ◽  
Dopaminergic Neurons ◽  
Cell Activation ◽  
Cell Loss ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Mice Model ◽  
Glial Cell Activation ◽  
6 Hydroxydopamine ◽  
First Time

Several lines of investigation have implicated oxidative stress in Parkinson’s disease (PD) pathogenesis, but the mechanisms involved are still unclear. In this study, we characterized the involvement of NADPH oxidase (Nox), a multisubunit enzyme that catalyzes the reduction of oxygen, in the 6-hydroxydopamine- (6-OHDA-) induced PD mice model and compared for the first time the effects of this neurotoxin in mice lackinggp91phox-/-, the catalytic subunit of Nox2, and pharmacological inhibition of Nox with apocynin. Six-OHDA induced increased protein expression ofp47phox, a Nox subunit, in striatum.gp91phox-/-mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited neuroprotection. Wt mice treated with apocynin andgp91phox-/-mice both exhibited ameliorated apomorphine-induced rotational behavior. The microglial activation observed within the striatum and the substantia nigra pars compacta (SNpc) of 6-OHDA-injected Wt mice was prevented by apocynin treatment and was not detected ingp91phox-/-mice. Apocynin was not able to attenuate astrocyte activation in SN. The results support a role for Nox2 in the 6-OHDA-induced degeneration of dopaminergic neurons and glial cell activation in the nigrostriatal pathway and reveal that no comparable 6-OHDA effects were observed between apocynin-treated andgp91phox-/-mice groups.

Distribution of GABA-like immunoreactive neurons and fibers in the central visual nuclei and retina of frog, Rana pipiens

1998 ◽  
Vol 15 (6) ◽  
pp. 995-1006 ◽  
Author(s):  
ZHENG LI ◽  
KATHERINE V. FITE
Keyword(s):  
Rana Pipiens ◽  
Thalamic Nucleus ◽  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Outer Nuclear Layer ◽  
Nerve Fibers ◽  
Retinal Ganglion ◽  
Gamma Aminobutyric Acid ◽  
Double Labeling ◽  
Retinal Terminal

Immunocytochemistry was used to study the distribution of gamma-aminobutyric acid (GABA) throughout the central visual nuclei and retina in Rana pipiens. In the retina, GABA immunoreactivity (both somata and fibers) was observed in all layers except the outer nuclear layer (ONL). Contrary to earlier reports, about 30% of total neurons within ganglion cell layer (GCL) expressed GABA immunoreactivity. Double-labeling studies indicated that about half of the GABA-containing perikarya in the GCL were retinal ganglion cells (RGCs). In the diencephalon, intensely labeled GABA-immunoreactive neurons and nerve fibers were observed within the neuropil of Bellonci (nB) and corpus geniculatum (CG), while only immunoreactive puncta were found in the rostral visual nucleus (RVN). In the pretectal region, the posterior thalamic nucleus (nPT) contained the most intensely labeled GABA immunoreactive perikarya and nerve fibers in the entire brain. Lightly immunoreactive perikarya were also found in the large-celled nucleus lentiformis mesencephali (nLM), as well as in the pretectal gray, which contains neurons postsynaptic to the retinal terminal zones within nLM. In the optic tectum (OT), both immunoreactive perikarya and fibers were found within superficial layers 8 and 9, whereas only densely packed immunoreactive perikarya were evident in the deep tectal layers (i.e. 2, 4, 6). The nucleus of the basal optic root (nBOR) contained a small number of lightly labeled GABA-immunoreactive perikarya, mostly located in the dorsal half of the nucleus. A large number of perikarya within the nucleus isthmi (NI) were also immunostained.

No age-related cell loss in three retinal nuclear layers of the Long-Evans rat

2007 ◽  
Vol 24 (6) ◽  
pp. 799-803 ◽  
Author(s):  
LIXIA FENG ◽  
ZHAOXIA SUN ◽  
HUI HAN ◽  
YIFENG ZHOU ◽  
MING ZHANG
Keyword(s):  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Outer Nuclear Layer ◽  
Photoreceptor Cells ◽  
Cell Loss ◽  
Related Cell ◽  
Age Related ◽  
Long Evans ◽  
Number Of Cells

The retina mainly contains ganglion, bipolar and photoreceptor cells which are distributed in the ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL), respectively. Whether there is an age-related loss of these retinal cells remains not well understood. Cell density and the total number of cells were two commonly used measures to evaluate such age-related changes in most previous studies and provided controversial conclusions. The use of density measures as decisive data is problematic because the total area of the retina was expanded in aging, whereas the application of the total number of cells was limited for assessing ganglion cells. In this study, thus, we wanted to test whether there is an age-related cell loss in the GCL, INL and ONL and if so, whether such a loss is correlated to the convergence ratio of these cells. We used stereological procedures to quantify the total number of cells in the three retinal nuclear layers in six young and six aged Long-Evans rats. We found that during aging, the total volume of the retina remained unchanged, but the retina became thinner. There was no cell loss in each individual nuclear layer, and the ratio of the ONL to INL to GCL was preserved.

scholarly journals Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice

2005 ◽  
Vol 171 (2) ◽  
pp. 313-325 ◽  
Author(s):  
Tatjana C. Jakobs ◽  
Richard T. Libby ◽  
Yixin Ben ◽  
Simon W.M. John ◽  
Richard H. Masland
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Optic Nerve Head ◽  
Ganglion Cells ◽  
Mechanical Damage ◽  
Cell Loss ◽  
Cell Types ◽  
Retinal Neurons ◽  
Cell Degeneration

Using a variety of double and triple labeling techniques, we have reevaluated the death of retinal neurons in a mouse model of hereditary glaucoma. Cell-specific markers and total neuron counts revealed no cell loss in any retinal neurons other than the ganglion cells. Within the limits of our ability to define cell types, no group of ganglion cells was especially vulnerable or resistant to degeneration. Retrograde labeling and neurofilament staining showed that axonal atrophy, dendritic remodeling, and somal shrinkage (at least of the largest cell types) precedes ganglion cell death in this glaucoma model. Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors. Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration. However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

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.

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