Dendritic competition in the developing retina: Ganglion cell density gradients and laterally displaced dendrites

1993 ◽  
Vol 10 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Rafael Linden
Keyword(s):  
Density Gradient ◽  
Cell Density ◽  
Time Course ◽  
Ganglion Cells ◽  
Lateral Displacement ◽  
Optic Tract ◽  
Density Gradients ◽  
Temporal Asymmetry ◽  
Dendritic Arbors ◽  
Contralateral Eye

AbstractDendrites of retinal ganglion cells (RGCs) tend to be distributed preferentially toward areas of reduced RGC density. This, however, does not occur in the retina of normal pigmented rats, in which it has been suggested that the centro-peripheral gradient of RGC density is too shallow to provide directional guidance to growing dendrites. In this study, laterally displaced dendrites of RGCs retrogradely labeled with horseradish peroxidase were related to cell density gradients induced experimentally in the rat retina. Neonatal unilateral lesions of the optic tract produced retrograde degeneration of contralaterally projecting RGCs, but spared ipsilaterally projecting neurons in the same retina. These lesions created an anomalous temporal to nasal gradient of cell density across the decussation line, opposite to the nasal to temporal gradient found along the same axis in either normal rats or rats that had the contralateral eye removed at birth. RGCs in rats that received optic tract lesions had their dendrites displaced laterally toward the depleted nasal retina, while in either normal or enucleated rats there was no naso-temporal asymmetry. The lateral displacement affected both primary dendrites and higher-order branches. However, the gradient of cell density after optic tract lesions was less steep than the gradient in either normal or enucleated rats. To test for the presence of steeper gradients at early stages of development, RGC density gradients were also examined at postnatal day 5 (P5). In normal rats, the RGCs were homogeneously distributed throughout the retina, while rats given optic tract lesions at birth already showed a temporo-nasal density gradient at P5. Still, this anomalous gradient was less steep than that found in normal adults. It is concluded that the time course, rather than the steepness of the RGC density gradient, is the major determinant of the lateral displacement of dendritic arbors with respect to the soma in developing RGCs. The data are consistent with the idea that the overall shape of dendritic arbors depends in part on dendritic competition during retinal development.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

Cell density affects spreading and clustering, but not attachment, of human keratinocytes in serum-free medium

1991 ◽  
Vol 99 (2) ◽  
pp. 387-395
Author(s):  
M. Malcovati ◽  
M.L. Tenchini
Keyword(s):  
Cell Density ◽  
Time Course ◽  
Cluster Formation ◽  
Physicochemical Characterization ◽  
Human Keratinocytes ◽  
Conditioned Media ◽  
Serum Free Medium ◽  
Free Medium ◽  
Spreading Factor ◽  
Serum Free

Attachment, spreading and clustering of second-passage human human keratinocytes in serum-free medium have been evaluated within 24 h after plating, as a function of the density of the inoculum and of time, in two different strains. The results show that attachment is unaffected by cell density and differs significantly from strain to strain. Cell density affects the distribution of attached keratinocytes among three morphologically distinct classes: unspread, spread and clustered cells. The percentage of unspread keratinocytes shows a linear decrease at increasing cell density, and that of spread keratinocytes an increase, resulting from statistically significant increases in the percentages of both single and clustered cells. Spreading on uncoated surfaces appears therefore as an inducible phenomenon. The use of media conditioned by keratinocytes, fibroblasts and HeLa cells shows that keratinocytes specifically secrete a diffusible ‘spreading factor’. We term this phenomenon ‘autocrine induced spreading’. Preliminary physicochemical characterization suggests that a protein could be responsible for the spreading activity of conditioned media. The ‘spreading factor’ seems to act directly on the cells, and not through a modification of the plastic surface of the dishes, since most (greater than 70%) of the spreading activity can be recovered in the conditioned media used in pre-coating experiments. The percentages of clusters follow ‘saturation’ kinetics at increasing cell density, while the percentage of clustered cells increases linearly with the density of inoculum. Time-course experiments show that the rate of spreading is cell density- and strain-independent. The percentages of clusters and of total clustered cells are time-independent, suggesting that cluster formation takes place in suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

The retinal ganglion cell distribution and the representation of the visual field in area 17 of the owl monkey, Aotus trivirgatus

1993 ◽  
Vol 10 (5) ◽  
pp. 887-897 ◽  
Author(s):  
L. C. L. Silveira ◽  
V. H. Perry ◽  
E. S. Yamada
Keyword(s):  
Visual Cortex ◽  
Visual Field ◽  
Ganglion Cell ◽  
Cell Density ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Temporal Region ◽  
Cell Distribution ◽  
Area 17 ◽  
Displaced Amacrine Cells

AbstractThe distribution of ganglion cells and displaced amacrine cells was determined in whole-mounted Aotus retinae. In contrast to diurnal simians, Aotus has only a rudimentary fovea. Ganglion cell density decreases towards the periphery at approximately the same rate along all meridians, but is 1.2–1.8 times higher in the nasal periphery when compared to temporal region at the same eccentricities. The total number of ganglion cells varied from 421,500 to 508,700. Ganglion cell density peaked at 15,000/mm2 at 0.25 mm dorsal to the fovea. The displaced amacrine cells have a shallow density gradient, their peak density in the central region is about 1500–2000/mm2 and their total number varied from 315,900 to 482,800. Comparison between ganglion cell density and areal cortical magnification factor for the primary visual cortex, area 17, shows that there is not a simple proportional representation of the ganglion cell distribution. There is an overrepresentation of the central 10 deg of the visual field in the visual cortex. The present results for Aotus and the results of a similar analysis of data from other primates indicate that the overrepresentation of the central visual field is a general feature of the visual system of primates.

scholarly journals B205 The relation between direction of cell migration and cell density gradient in the formation of cartilage cell aggregation

2012 ◽  
Vol 2012.23 (0) ◽  
pp. 135-136
Author(s):  
Kenji Isshiki ◽  
Akihisa Otaka ◽  
Kazuya Takahashi ◽  
Katsura Kojima ◽  
Yasushi Tamada ◽  
...  
Keyword(s):  
Cell Migration ◽  
Density Gradient ◽  
Cell Density ◽  
Cell Aggregation ◽  
Cartilage Cell

scholarly journals Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

2013 ◽  
Vol 109 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Jessica L. Hauser ◽  
Eleanore B. Edson ◽  
Bryan M. Hooks ◽  
Chinfei Chen
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Time Course ◽  
Ganglion Cells ◽  
Glutamate Transporters ◽  
Decay Kinetics ◽  
Metabotropic Glutamate ◽  
Glutamate Concentration ◽  
Group Ii ◽  
Retinogeniculate Synapse

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.

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.

Abnormally high variability in the uncrossed retinofugal pathway of mice with albino mosaicism

Development ◽  
1987 ◽  
Vol 101 (4) ◽  
pp. 857-867 ◽  
Author(s):  
R.W. Guillery ◽  
G. Jeffery ◽  
B.M. Cattanach
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Gene Dosage ◽  
Optic Tract ◽  
High Variability ◽  
Retinal Ganglion ◽  
Rare Occurrence ◽  
Autosome Translocation ◽  
Open Question ◽  
The Relationship

Female mice showing albino mosaicism due to an X-autosome translocation [Is(In7;X)Ct] have been studied in order to investigate the relationship between the distribution of melanin and the formation, early in development, of the abnormally small uncrossed retinofugal pathway characteristically found in all albino mammals. Earlier evidence indicates that cells normally bearing melanin play a role in producing the abnormality. In the mosaic mice, the albino gene is expressed in only about half of the cells due to random X-inactivation and the patches of normal and albino cells are extremely small relative to total retinal size (less than 1/50). We argued that if all the cells that would normally bear melanin play a role in producing the albino abnormality then the mosaic mice would have a pathway abnormality, about half the size of that in the albino mice. If, however, only a small patch of these cells plays a role, as has been proposed in earlier studies, then one would expect the size of the uncrossed pathway to be highly variable in the mosaic mice. The size of the uncrossed pathway was assessed by placing horseradish peroxidase in the region of the optic tract and lateral geniculate nucleus unilaterally and then counting the number of retrogradely labelled retinal ganglion cells on the same side. The mosaic mice showed a highly variable uncrossed pathway. In some of the mosaic mice, it was the same size as in the albinos and, in others, it was the same size as in normally pigmented mice. Surprisingly, in a small number of mosaic mice, the uncrossed pathway was larger than normal. Whether this relatively rare occurrence of a supernormal uncrossed pathway is due to the higher gene dosage or to the translocation itself remains an open question.

Corneal Endothelial Cell Density After Femtosecond Thin-Flap LASIK and PRK for Myopia: A Contralateral Eye Study

2009 ◽  
Vol 25 (12) ◽  
pp. 1098-1102 ◽  
Author(s):  
Ryan T. Smith ◽  
George O. Waring ◽  
Daniel S. Durrie ◽  
Jason E. Stahl ◽  
Priscilla Thomas
Keyword(s):  
Endothelial Cell ◽  
Cell Density ◽  
Corneal Endothelial Cell ◽  
Endothelial Cell Density ◽  
Corneal Endothelial Cell Density ◽  
Contralateral Eye

Visual receptive field properties in kitten pretectal nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract

1993 ◽  
Vol 70 (2) ◽  
pp. 814-827 ◽  
Author(s):  
C. Distler ◽  
K. P. Hoffmann
Keyword(s):  
Discharge Rate ◽  
Age Groups ◽  
Optic Tract ◽  
Visual Response ◽  
Stimulus Movement ◽  
Cortical Input ◽  
Preferred Direction ◽  
Pretectal Nucleus ◽  
Adult Cats ◽  
Contralateral Eye

1. Neurons in the pretectal nucleus of the optic tract (NOT) and dorsal terminal nucleus of the accessory optic tract (DTN) were recorded in anesthetized and paralyzed kittens on postnatal days 18 to 48 (P18-P48) as well as in adult cats. 2. Spontaneous as well as stimulus driven discharge rates of NOT-DTN neurons in the youngest kittens (P18-P23) are significantly lower than in older kittens (P27-P33) or adult cats. 3. Visual latencies of NOT-DTN neurons in P18-P23 kittens are significantly longer than in P27-P33 kittens. They further decrease as the animals reach adulthood. 4. Already in the youngest animals recorded in this experimental series (P18) NOT-DTN neurons were selective for ipsiversive horizontal stimulus movement. When expressed as the difference between response strength during stimulation in the preferred and the nonpreferred direction, P18-P23 NOT-DTN neurons are less direction selective than NOT-DTN cells in older animals. However, the normalized directional tuning expressed as percent change in discharge rate per degree change in stimulus direction away from the preferred direction (where discharge rate is set 100%) is about equal in all age groups. 5. NOT-DTN neurons in P18-P23 kittens respond to a rather limited range of stimulus speeds with an optimum at approximately 10 degrees/s. In P27-P33 kittens, NOT-DTN neurons increase their responsive range to higher stimulus speeds. As the animals approach adulthood, the range of effective stimulus speeds further broadens to include very low ones. 6. In P18-P23 kittens, the majority of NOT-DTN neurons is exclusively activated by the contralateral eye; only a few neurons receive an additional input from the ipsilateral eye. In P27-P48 kittens, the influence of the ipsilateral eye has significantly increased but with the majority of NOT-DTN cells still being dominated by the contralateral eye. Finally, in adults, a further strengthening of the ipsilateral input leads to a more binocularly balanced input to NOT-DTN cells. 7. Electrical stimulation in areas 17 and 18 did not elicit orthodromic action potentials in NOT-DTN neurons before P27. Thus the cortical input to the NOT-DTN in kittens becomes functional only at 4 wk of age. 8. In conclusion, the significant changes of visual response properties of NOT-DTN neurons coincide with the time when the cortical input to the NOT-DTN becomes functional.(ABSTRACT TRUNCATED AT 400 WORDS)

Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-β receptor and Src

2003 ◽  
Vol 285 (3) ◽  
pp. H1081-H1090 ◽  
Author(s):  
Shu Q. Liu ◽  
Christopher Tieche ◽  
Dalin Tang ◽  
Paul Alkema
Keyword(s):  
Shear Stress ◽  
Smooth Muscle ◽  
Cell Density ◽  
Fluid Shear Stress ◽  
Density Gradients ◽  
Dependent Manner ◽  
Fluid Shear ◽  
Polymer Implants ◽  
Β Receptor

Blood vessels are subject to fluid shear stress, a hemodynamic factor that inhibits the mitogenic activities of vascular cells. The presence of nonuniform shear stress has been shown to exert graded suppression of cell proliferation and induces the formation of cell density gradients, which in turn regulate the direction of smooth muscle cell (SMC) migration and alignment. Here, we investigated the role of platelet-derived growth factor (PDGF)-β receptor and Src in the regulation of such processes. In experimental models with vascular polymer implants, SMCs migrated from the vessel media into the neointima of the implant under defined fluid shear stress. In a nonuniform shear model, blood shear stress suppressed the expression of PDGF-β receptor and the phosphorylation of Src in a shear level-dependent manner, resulting in the formation of mitogen gradients, which were consistent with the gradient of cell density as well as the alignment of SMCs. In contrast, uniform shear stress in a control model elicited an even influence on the activity of mitogenic molecules without modulating the uniformity of cell density and did not significantly influence the direction of SMC alignment. The suppression of the PDGF-β receptor tyrosine kinase and Src with pharmacological substances diminished the gradients of mitogens and cell density and reduced the influence of nonuniform shear stress on SMC alignment. These observations suggest that PDGF-β receptor and Src possibly serve as mediating factors in nonuniform shear-induced formation of cell density gradients and alignment of SMCs in the neointima of vascular polymer implants.

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