scholarly journals Tbr2-expressing retinal ganglion cells are ipRGCs

2020 ◽  
Author(s):  
Chai-An Mao ◽  
Ching-Kang Chen ◽  
Takae Kiyama ◽  
Nicole Weber ◽  
Christopher M. Whitaker ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Primary Component ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
T Box ◽  
Retinofugal Projections ◽  
A Minor

AbstractThe mammalian retina contains more than 40 retinal ganglion cell (RGC) subtypes based on their unique morphologies, functions, and molecular profiles. Among them, intrinsically photosensitive RGCs (ipRGCs) are the first specified RGC type that emerged from a common pool of retinal progenitor cells. Previous work has shown that T-box transcription factor T-brain 2 (Tbr2) is essential for the formation and maintenance of ipRGCs, and Tbr2-expressing RGCs activate Opn4 expression upon native ipRGC loss, suggesting that Tbr2+ RGCs can serve as a reservoir for ipRGCs. However, the identity of Tbr2+ RGCs has not been fully vetted, and the developmental and molecular mechanisms underlying the formation of native and reservoir ipRGCs remain unclear. Here, we showed that Tbr2-expressing retinal neurons include RGCs and GABAergic displaced amacrine cells (dACs). Using genetic sparse labeling, we demonstrated that the majority of Tbr2+ RGCs are intrinsically photosensitive and morphologically indistinguishable from known ipRGC types and have identical retinofugal projections. Additionally, we found a minor fraction of Pou4f1-expressing Tbr2+ RGCs marks a unique OFF RGC subtype. Most of the Tbr2+ RGCs can be ablated by anti-melanopsin-SAP toxin in adult retinas, supporting that Tbr2+ RGCs contain reservoir ipRGCs that express melanopsin at varying levels. When Tbr2 is deleted in adult retinas, Opn4 expression is diminished followed by the death of Tbr2-deficient cells, suggesting that Tbr2 is essential for both Opn4 expression and ipRGC survival. Finally, Tbr2 extensively occupies multiple T-elements in the Opn4 locus, indicating a direct regulatory role for Tbr2 on Opn4 transcription.Significance statementMelanopsin/Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play fundamental roles in non-image forming vision. Previously we identified Tbr2 as the key transcription regulator for the development and maintenance of ipRGCs. To reveal the full identity of Tbr2-expressing retinal neurons and how Tbr2 acts, we generated a novel mouse line to genetically label and study Tbr2-expressing cells. Our in-depth characterizations firmly established that most Tbr2+ RGCs are indeed ipRGCs and that Tbr2 regulates Opn4 transcription, thus place Tbr2-Opn4 transcription regulatory hierarchy as the primary component in the development and maintenance of the non-image forming visual system.

scholarly journals Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

2014 ◽  
Vol 25 (2) ◽  
pp. 234-244 ◽  
Author(s):  
Chizu Nakamoto ◽  
Soh-Leh Kuan ◽  
Amy S. Findlay ◽  
Elaine Durward ◽  
Zhufeng Ouyang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neuronal Cell ◽  
Amacrine Cells ◽  
Progression Rate ◽  
Retinal Ganglion ◽  
Displaced Amacrine Cells

For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development.

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 Expression of a Barhl1a reporter in subsets of retinal ganglion cells and commissural neurons of the developing zebrafish brain

2020 ◽  
Author(s):  
Shahad Albadri ◽  
Olivier Armant ◽  
Tairi Aljand-Geschwill ◽  
Filippo Del Bene ◽  
Matthias Carl ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Commissural Neurons ◽  
Axonal Projections ◽  
Underlying Mechanisms ◽  
And Function

AbstractPromoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, only barhl2 is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated the barhl1a and barhl2 paralogues. In the Zebrafish retina, Barhl2 functions as determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast, barhl1a expression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a:GFP reporter line in vivo showing that Barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of Barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.

Characterization of Spontaneous Inhibitory Synaptic Currents in Salamander Retinal Ganglion Cells

1998 ◽  
Vol 80 (4) ◽  
pp. 1752-1764 ◽  
Author(s):  
Fan Gao ◽  
Samuel M. Wu
Keyword(s):  
Retinal Ganglion Cells ◽  
Synaptic Vesicles ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Equilibrium Potential ◽  
Retinal Ganglion ◽  
Light Onset ◽  
Synaptic Currents ◽  
Postsynaptic Currents

Gao, Fan and Samuel M. Wu. Characterization of spontaneous inhibitory synaptic currents in salamander retinal ganglion cells. J. Neurophysiol. 80: 1752–1764, 1998. Spontaneous and light-evoked postsynaptic currents (sPSCs and lePSCs, respectively) in retinal ganglion cells of the larval tiger salamander were recorded under voltage-clamp conditions from living retinal slices. The focus of this study is to characterize the spontaneous inhibitory PSCs (sIPSCs) and their contribution to the light-evoked inhibitory PSCs (leIPSCs) in on-off ganglion cells. sIPSCs were isolated from spontaneous excitatory PSCs (sEPSCs) by application of 10 μM 6,7-dinitroquinoxaline-2,3-dione (DNQX) + 50 μM 2-amino-5-phosphonopentanoic acid (AP5). In ∼70% of on-off ganglion cells, bicuculline (or picrotoxin) completely blocks sIPSCs, suggesting all sIPSCs in these cells are mediated by GABAergic synaptic vesicles and γ-aminobutyric acid-A (GABAA) receptors (GABAergic sIPSCs, or GABAsIPSCs). In the remaining 30% of on-off ganglion cells, bicuculline (or picrotoxin) blocks 70–98% of the sIPSCs, and the remaining 2–30% are blocked by strychnine (glycinergic sIPSCs, or GLYsIPSCs). GABAsIPSCs occur randomly with an exponentially distributed interval probability density function, and they persist without noticeable rundown over time. The GABAsIPSC frequency is greatly reduced by cobalt, consistent with the idea that they are largely mediated by calcium-dependent vesicular release. GABAsIPSCs in DNQX + AP5 are tetrodotoxin (TTX) insensitive, suggesting that amacrine cells that release GABA under these conditions do not generate spontaneous action potentials. The average GABAsIPSCs exhibited linear current-voltage relation with a reversal potential near the chloride equilibrium potential, and an average peak conductance of 319.67 ± 252.83 (SD) pS. For GLYsIPSCs, the average peak conductance increase is 301.68 ± 94.34 pS. These parameters are of the same order of magnitude as those measured in inhibitory miniature postsynaptic currents (mIPSCs) associated with single synaptic vesicles in the CNS. The amplitude histograms of GABAsIPSCs did not exhibit multiple peaks, suggesting that the larger events are not discrete multiples of elementary events (or quanta). We propose that each GABAsIPSC or GLYsIPSC in retinal ganglion cells is mediated by a single or synchronized multiple of synaptic vesicles with variable neurotransmitter contents. In a sample of 16 on-off ganglion cells, the average peak leIPSC (held at 0 mV) at the light onset is 509.0 ± 233.85 pA and that at the light offset is 529.0 ± 339.88 pA. The approximate number of GABAsIPSCs and GLYsIPSCs required to generate the average light responses, calculated by the ratio of the charge (area under current traces) of the leIPSCs to that of the average single sIPSCs, is 118 ± 52 for the light onset, and 132 ± 76 for the light offset.

scholarly journals Architecture of retinal projections to the central circadian pacemaker

2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Microscopic Analysis ◽  
Brain Regions ◽  
Retinal Ganglion ◽  
Circadian Pacemaker ◽  
Retinal Neurons ◽  
Retinal Input ◽  
Innervation Patterns ◽  
Left And Right

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.

A quantitative analysis of the effects of excitatory neurotoxins on retinal ganglion cells in the chick

1990 ◽  
Vol 4 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Ngoh Ngoh Tung ◽  
Ian G. Morgan ◽  
David Ehrlich
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Small Cells ◽  
Retinal Ganglion ◽  
Chick Retina ◽  
Area 5 ◽  
Different Types ◽  
Displaced Amacrine Cells ◽  
Series Of Experiments

AbstractThe present study examines the differential effects of three excitotoxins, kainic acid (KA), N-methyl-D-aspartate (NMDA), and α-amino-2,3-amino-2,3-dihydro-5- methyl-3-oxo-4- isoxazolepropanoic acid (AMPA) on neurons within the genglion cell layer (GCL) of the chick retina. Two-day-old chicks were given a single, 5 μl, intravitreal injection of KA, NMDA, or AMPA at a range of doses. Following treatment with 40 nmol KA, there was a 21% loss of neurons in the GCL. At 200 nmol KA, the loss increased to 46%. Exposure to KA eliminated mainly small neurons of soma area 5–15μm2, and medium-sized ganglion cells of soma area 15–25μm2. Large ganglion cells (>25μ,2) remained unaffected. The vast majority of small cells were probably displaced amarcrine cells. At a does of 3000 nmol NMDA, no further loss of cells was evident. Exposure to 200 nmol AMPA resulted in a 30% loss of large and some medium-sized ganglion cells. In a further series of experiments, exposure to excitotoxin was followed by a retinal scratch, which eliminated retinal ganglion cells within the axotomized region. The results indicate that only a small proportion of displaced amacrine cells are destroyed by NMDA and AMPA, whereas virtually all displaced amarine cells are sensitive to KA. The findings of this study indicate the existence of subclasses of ganglion cells with specificity towards different types of excitatory amino acids (EAA).

Neuroactive peptides as markers of retinal ganglion cell populations that differ in anatomical organization and function

1988 ◽  
Vol 1 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Rodrigo O. Kuljis ◽  
Harvey J. Karten
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Pharmacological Manipulation ◽  
Functional Aspects ◽  
Neuroactive Peptides ◽  
Retinofugal Projections ◽  
And Function

AbstractRecent immunocytochemical studies indicate the existence of several classes of peptide- (PRGC) and catecholamine-containing retinal ganglion cells in anurans, birds, and mammals. Different classes of PRGC project to discrete and seemingly unique layers in the retino-recipient portion of the anuran and avian optic tectum. Peptide-containing retinofugal projections to the frog tectum originate early in development, and are reestablished by some classes of PRGC during regeneration of the optic nerve. These findings indicate that chemically specific, parallel retinofugal pathways presumably subserve different functional aspects of vision in vertebrates. Exciting prospects for research include the correlation of physiologically with immunocytochemically defined classes of retinal ganglion cells, the analysis of the possible role of neuroactive peptides in retinofugal transmission, and the pharmacological manipulation of putative peptidergic retinofugal pathways to analyze their role in visual function.

scholarly journals Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149501 ◽  
Author(s):  
Anton Delwig ◽  
DeLaine D. Larsen ◽  
Douglas Yasumura ◽  
Cindy F. Yang ◽  
Nirao M. Shah ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinofugal Projections

scholarly journals Radial migration: Retinal neurons hold on for the ride

2016 ◽  
Vol 215 (2) ◽  
pp. 147-149 ◽  
Author(s):  
Jeremy N. Kay
Keyword(s):  
Nervous System ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Newborn Neuron ◽  
Radial Migration ◽  
Biological Basis ◽  
Cell Biol

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.

scholarly journals Transcriptional logic of cell fate specification and axon guidance in early born retinal neurons revealed by single-cell mRNA profiling

2018 ◽  
Author(s):  
Quentin Lo Giudice ◽  
Marion Leleu ◽  
Pierre J. Fabre
Keyword(s):  
Axon Guidance ◽  
Cell Fate ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Retinal Ganglion ◽  
Cell Fate Specification ◽  
Retinal Neurons ◽  
Fate Specification ◽  
Guidance Cues ◽  
Insight Into

ABSTRACTRetinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.

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