scholarly journals Multi-species single-cell transcriptomic analysis of ocular compartment regulons

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pradeep Gautam ◽  
Kiyofumi Hamashima ◽  
Ying Chen ◽  
Yingying Zeng ◽  
Bar Makovoz ◽  
...  
Keyword(s):  
Single Cell ◽  
Retinal Ganglion Cells ◽  
Adult Stem Cells ◽  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Integrative Research ◽  
Sequencing Studies ◽  
Ligand Interactions ◽  
Multiple Species

AbstractThe retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells.

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.

scholarly journals Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis

2020 ◽  
Vol 117 (19) ◽  
pp. 10339-10349 ◽  
Author(s):  
Tavé van Zyl ◽  
Wenjun Yan ◽  
Alexi McAdams ◽  
Yi-Rong Peng ◽  
Karthik Shekhar ◽  
...  
Keyword(s):  
Single Cell ◽  
Aqueous Humor ◽  
Ganglion Cells ◽  
Anterior Segment ◽  
Experimental Studies ◽  
Cynomolgus Macaque ◽  
Cell Types ◽  
Model Systems ◽  
Retinal Ganglion ◽  
Aqueous Humor Outflow

Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa), and mouse (Mus musculus). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.

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.

scholarly journals Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells

2009 ◽  
Vol 101 (4) ◽  
pp. 1972-1987 ◽  
Author(s):  
Shelley I. Fried ◽  
Aaron C. W. Lasker ◽  
Neal J. Desai ◽  
Donald K. Eddington ◽  
Joseph F. Rizzo
Keyword(s):  
Sodium Channel ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Electric Stimulation ◽  
Ganglion Cells ◽  
Cell Types ◽  
Threshold Region ◽  
Retinal Ganglion ◽  
Neural Prosthetic ◽  
Voltage Gated Sodium Channels

Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 μm from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed.

Retinal ganglion cells projecting to the optic tectum and visual thalamus of lizards

2002 ◽  
Vol 19 (5) ◽  
pp. 575-581 ◽  
Author(s):  
ALINO MARTINEZ-MARCOS ◽  
ENRIQUE LANUZA ◽  
FERNANDO MARTINEZ-GARCIA
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Cell Types ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Visual Thalamus ◽  
Podarcis Hispanica

Retinal ganglion cells projecting to the optic tectum and visual thalamus have been investigated in the lizard, Podarcis hispanica. Injections of biotinylated dextran-amine in the optic tectum reveal seven morphological cell varieties including one displaced ganglion cell type. Injections in the visual thalamus yield similar ganglion cell classes plus four giant ganglion cells, including two displaced ganglion cell types. The present study constitutes the first comparison of tectal versus thalamic ganglion cell types in reptiles. The situation found in lizards is similar to that reported in mammals and birds where some cell types projecting to the thalamus are larger than those projecting to the mesencephalic roof. The presence of giant retino-thalamic ganglion cells with specific dendritic arborizations in sublaminae A and B of the inner plexiform layer suggests that parts of the visual thalamus of lizards could be implicated in movement detection, a role that might be played by the ventral lateral geniculate nucleus, which is involved in our tracer injections.

scholarly journals Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Bruce A. Rheaume ◽  
Amyeo Jereen ◽  
Mohan Bolisetty ◽  
Muhammad S. Sajid ◽  
Yue Yang ◽  
...  
Keyword(s):  
Single Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Transcriptome Profiling ◽  
Retinal Ganglion ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Categorization of Physiologically and Morphologically Characterized non-α/non-β Cat Retinal Ganglion Cells Using Fractal Geometry

Fractals ◽  
1997 ◽  
Vol 05 (04) ◽  
pp. 673-684 ◽  
Author(s):  
H. F. Jelinek ◽  
I. Spence
Keyword(s):  
Fractal Dimension ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Cell Type ◽  
Box Counting ◽  
Standard Values ◽  
Box Counting Method ◽  
Delta Cells

Non-α/non-β cat retinal ganglion cell images were obtained from the published literature, and a homogeneous group of cells was chosen as a standard for each currently accepted cell type (γ, δ and ε). The NIH box-counting method was chosen to determine the fractal dimension (Df) of all cells. The 'standard' values allowed comparisons with other morphologically and physiologically non-α/non-β classified cell types in the literature. We suggest, based on fractal analysis of the dendritic trees, that the morphologically defined γ, δ, and ε cells are distinct types. The W-tonic and W-phasic cell types were further divided into 2 subcategories (W-tonic1, W-tonic2, W-phasic1, W-phasic2). The fractal dimension, of the ε cells being equivalent to the W-tonic1 group and γ cell type equivalent to the W-phasic1 group. Delta cells may be equivalent to either the W-tonic2 or the W-phasic2 group. We discuss the value of the fractal dimension as an added morphological parameter for future morphophysiological classification schemes of vertebrate retinal ganglion cells.

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