scholarly journals Laminin receptors in the retina: sequence analysis of the chick integrin alpha 6 subunit. Evidence for transcriptional and posttranslational regulation.

1991 ◽  
Vol 113 (2) ◽  
pp. 405-416 ◽  
Author(s):  
I de Curtis ◽  
V Quaranta ◽  
R N Tamura ◽  
L F Reichardt
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Developmental Regulation ◽  
Cell Types ◽  
Laminin Receptor ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Laminin Receptors ◽  
Chick Retina ◽  
Integrin Alpha 6

The integrin alpha 6 beta 1 is a prominent laminin receptor used by many cell types. In the present work, we isolate clones and determine the primary sequence of the chick integrin alpha 6 subunit. We show that alpha 6 beta 1 is a prominent integrin expressed by cells in the developing chick retina. Between embryonic days 6 and 12, both retinal ganglion cells and other retinal neurons lose selected integrin functions, including the ability to attach and extend neurites on laminin. In retinal ganglion cells, we show that this is correlated with a dramatic decrease in alpha 6 mRNA and protein, suggesting that changes in gene expression account for the developmental regulation of the interactions of these neurons with laminin. In other retinal neurons the expression of alpha 6 mRNA and protein remains high while function is lost, suggesting that the function of the alpha 6 beta 1 heterodimer in these cells is regulated by posttranslational mechanisms.

scholarly journals Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons

2020 ◽  
Vol 22 (1) ◽  
pp. 369
Author(s):  
Susanne Bürger ◽  
Jie Meng ◽  
Annette Zwanzig ◽  
Mike Beck ◽  
Maik Pankonin ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Laminin Receptor ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Differential Survival ◽  
Hypoxic Conditions ◽  
Pigment Epithelium Derived Factor ◽  
Inhibition Of Angiogenesis

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.

Function and spatial distribution in developing chick retina of the laminin receptor alpha 6 beta 1 and its isoforms

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 377-388 ◽  
Author(s):  
I. de Curtis ◽  
L.F. Reichardt
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Laminin Receptor ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Retinal Cells ◽  
Retina Development ◽  
Receptor Alpha ◽  
Chick Retina

We have recently shown that the laminin-binding integrin receptor, alpha 6 beta 1, is prominently expressed in the developing chick retina, and its expression and activity are regulated during development on both retinal ganglion cells and other neural retinal cells. In the present study, we show that antibodies specific for the extracellular portion of the chick alpha 6 subunit dramatically inhibit interactions in vitro between embryonic day 6 neural retinal cells and laminin, showing that alpha 6 beta 1 functions as an important laminin receptor on developing retinal neurons. In previous work, we showed that alpha 6 mRNA levels on retinal ganglion cells decrease dramatically after E6 during the period that RGC axons innervate the optic tectum. In the present study, we show decreases in alpha 6 mRNA are not prevented by ablation of the optic tectum, indicating that tectal contact is not the major cause of this decrease. Within the embryonic retina, the alpha 6 subunit is codistributed, in part, with laminin, suggesting that it functions as a laminin receptor during retina development in vivo. Furthermore, two isoforms of the alpha 6 protein with distinct cytoplasmic domains generated by differential splicing have quite different distribution patterns in the retina, suggesting that these two isoforms may have different functions during retinal development.

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.

Developmental loss of functional laminin receptors on retinal ganglion cells is regulated by their target tissue, the optic tectum

Development ◽  
1989 ◽  
Vol 107 (2) ◽  
pp. 381-387 ◽  
Author(s):  
J. Cohen ◽  
V. Nurcombe ◽  
P. Jeffrey ◽  
D. Edgar
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Matrix Protein ◽  
Binding Assay ◽  
Ganglion Cells ◽  
Target Tissue ◽  
Retinal Ganglion ◽  
Loss Of Response ◽  
High Affinity ◽  
Laminin Receptors

The ability of chick retinal ganglion cells (RGCs) to extend neurites on tissue culture substrata of the extra-cellular matrix protein laminin is lost during embryonic development. In order to establish the mechanism responsible for the loss of response, the number of high affinity (KD 10(−9) M) laminin receptors on both the cell bodies and neurites of RGCs were determined throughout this period by a ligand binding assay using radio-labelled laminin. It was found that the loss of response paralleled a decrease in receptor numbers on both the cell bodies and the neurites of the RGCs. Bilateral tectal ablation at embryonic day 6 resulted in the subsequent maintenance of laminin-stimulated neurite outgrowth, together with a partial inhibition of the loss of laminin receptors. Thus, the loss of response of the RGCs to laminin reflects a decrease in the numbers of laminin receptors on these neurons, and furthermore, this down-regulation is in turn dependent on innervation of the target tissue.

The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5713-5724 ◽  
Author(s):  
K.L. McCabe ◽  
E.C. Gunther ◽  
T.A. Reh
Keyword(s):  
Cell Differentiation ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Receptor Activation ◽  
Peripheral Retina ◽  
Retinal Ganglion ◽  
Fgf Receptor ◽  
Chick Retina ◽  
Regular Arrays

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 μm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

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).

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 Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1759
Author(s):  
Xandra Pereiro ◽  
Adam M. Miltner ◽  
Anna La Torre ◽  
Elena Vecino
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Müller Cells ◽  
Cell Types ◽  
Conditioned Media ◽  
Retinal Ganglion ◽  
Muller Cells ◽  
Müller Glia

Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.

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