scholarly journals Mechanisms for persistent microphthalmia following ethanol exposure during retinal neurogenesis in zebrafish embryos

2007 ◽  
Vol 24 (3) ◽  
pp. 409-421 ◽  
Author(s):  
BHAVANI KASHYAP ◽  
LOGAN C. FREDERICKSON ◽  
DEBORAH L. STENKAMP
Keyword(s):  
Cell Death ◽  
Cell Differentiation ◽  
Model Organism ◽  
Cell Types ◽  
Ethanol Exposure ◽  
Retinal Cell ◽  
Zebrafish Embryos ◽  
Eye Size ◽  
Organ Systems ◽  
Retinal Neurogenesis

The exposure of the developing human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the visual system. One common phenotype seen in humans exposed to ethanol in utero is microphthalmia. The objective of this study was to describe the effects of ethanol during retinal neurogenesis in a model organism, the zebrafish, and to pursue the potential mechanisms by which ethanol causes microphthalmia. Zebrafish embryos were exposed to 1% or 1.5% ethanol from 24 to 48 h after fertilization, a period during which the retinal neuroepithelium undergoes rapid proliferation and differentiation to form a laminated structure composed of different retinal cell types. Ethanol exposure resulted in significantly reduced eye size immediately following the treatment, and this microphthalmia persisted through larval development. This reduced eye size could not entirely be accounted for by the accompanying general delay in embryonic development. Retinal cell death was only slightly higher in ethanol-exposed embryos, although cell death in the lens was extensive in some of these embryos, and lenses were significantly reduced in size as compared to those of control embryos. The initiation of retinal neurogenesis was not affected, but the subsequent waves of cell differentiation were markedly reduced. Even cells that were likely generated after ethanol exposure—rod and cone photoreceptors and Müller glia—were delayed in their expression of cell-specific markers by at least 24 h. We conclude that ethanol exposure over the time of retinal neurogenesis resulted in persistent microphthalmia due to a combination of an overall developmental delay, lens abnormalities, and reduced retinal cell differentiation.

scholarly journals The Rise of Retinal Organoids for Vision Research

2020 ◽  
Vol 21 (22) ◽  
pp. 8484 ◽  
Author(s):  
Kritika Sharma ◽  
Tim U. Krohne ◽  
Volker Busskamp
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Retinal Cell ◽  
Retinal Diseases ◽  
Organ Systems ◽  
Cell Sources ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field’s improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations.

scholarly journals Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation

2008 ◽  
Vol 237 (3) ◽  
pp. 758-767 ◽  
Author(s):  
M. Valeria Canto-Soler ◽  
Hu Huang ◽  
M. Soledad Romero ◽  
Ruben Adler
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Cell Types ◽  
Retinal Cell ◽  
Different Cell Types

scholarly journals Neurogenesis and Specification of Retinal Ganglion Cells

2020 ◽  
Vol 21 (2) ◽  
pp. 451 ◽  
Author(s):  
Kim Tuyen Nguyen-Ba-Charvet ◽  
Alexandra Rebsam
Keyword(s):  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Retinal Ganglion ◽  
Intrinsic Factors ◽  
Visual Deficits ◽  
Retinal Neurogenesis ◽  
Cell Niche

Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal progenitor cells (RPCs) able to produce these cell types in a specific and timely order? Here, we will review the different models of retinal neurogenesis proposed over the last decades as well as the extrinsic and intrinsic factors controlling it. We will then focus on the molecular mechanisms, especially the cascade of transcription factors that regulate, more specifically, RGC fate. We will also comment on the recent discovery that the ciliary marginal zone is a new stem cell niche in mice contributing to retinal neurogenesis, especially to the generation of ipsilateral RGCs. Furthermore, RGCs are composed of many different subtypes that are anatomically, physiologically, functionally, and molecularly defined. We will summarize the different classifications of RGC subtypes and will recapitulate the specification of some of them and describe how a genetic disease such as albinism affects neurogenesis, resulting in profound visual deficits.

scholarly journals Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors

2021 ◽  
Author(s):  
Kayla F. Titialii-Torres ◽  
Ann C. Morris
Keyword(s):  
Cell Differentiation ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Retinal Development ◽  
Cell Types ◽  
Maternal Diabetes ◽  
Retinal Cell ◽  
Optokinetic Responses ◽  
Maternal Glucose

Diabetes is linked to various long-term complications in adults, such as neuropathy, nephropathy, and diabetic retinopathy. Diabetes poses additional risks for pregnant women, because glucose passes across the placenta, and excess maternal glucose can result in diabetic embryopathy. While many studies have examined the teratogenic effects of maternal diabetes on fetal heart development, little is known about the consequences of maternal hyperglycemia on the development of the embryonic retina. To address this question, we investigated retinal development in two models of embryonic hyperglycemia in zebrafish. Strikingly, we found that hyperglycemic larvae displayed a significant reduction in photoreceptors and horizontal cells, whereas other retinal neurons were not affected. We also observed reactive gliosis and abnormal optokinetic responses in hyperglycemic larvae. Further analysis revealed delayed retinal cell differentiation in hyperglycemic embryos that coincided with increased reactive oxygen species (ROS). Our results suggest that embryonic hyperglycemia causes abnormal retinal development via altered timing of cell differentiation and ROS production, which is accompanied by visual defects. Further studies using zebrafish models of hyperglycemia will allow us to understand the molecular mechanisms underlying these effects.

Dual regulation of the glycogen phosphorylase 2 gene Dictyostelium discoideum: the effects of DIF-1, cAMP, NH3 and adenosine

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1169-1178 ◽  
Author(s):  
Y. Yin ◽  
P.V. Rogers ◽  
C.L. Rutherford
Keyword(s):  
Cell Death ◽  
Cell Differentiation ◽  
Glycogen Phosphorylase ◽  
Cell Types ◽  
Regulatory Function ◽  
Current Evidence ◽  
Stalk Cell ◽  
Developmentally Regulated ◽  
Camp Induction ◽  
Spore Cell

Cell differentiation in Dictyostelium results in the formation of two cell types, stalk and spore cells. The stalk cells undergo programmed cell death, whereas spore cells retain viability. The current evidence suggests that stalk cell differentiation is induced by Differentiation Inducing Factor (DIF), while spore cell differentiation occurs in response to cAMP. We have discovered the first developmentally regulated Dictyostelium gene, the glycogen phosphorylase gene 2 (gp2) gene, that can be induced by both DIF-1 and cAMP, suggesting the possibility of a new group of developmentally regulated genes that have DIF-1 and cAMP dual responsiveness. The gp2 gene was found to be expressed in both prestalk/stalk cells and prespore/spore cells. The DIF-1 competence of the gp2 gene required uninterrupted development, whereas the cAMP-competence for the gene required only starvation. Both DIF-1 and cAMP induction of the gene could be inhibited by NH3, a factor that is thought to act as a developmental signal in Dictyostelium. Another developmental signal, adenosine, was found to repress the DIF-1 induction of the gp2 gene. Two introns in the gp2 gene were examined for their involvement in the regulation of the gene, but no regulatory function was detected. A model for the regulation of the gp2 gene during the development is proposed.

scholarly journals Time-resolved expression analysis comparing two selective retinal cell ablation paradigms in zebrafish reveals shared and cell-specific regenerative regulatory networks

2020 ◽  
Author(s):  
Steven L. Walker ◽  
Guohua Wang ◽  
Kevin B. Emmerich ◽  
Fang Wang ◽  
David T. White ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regulatory Networks ◽  
Model Organism ◽  
Cell Loss ◽  
Cell Types ◽  
Retinal Cell ◽  
Specific Cell ◽  
Retinal Regeneration ◽  
Cell Degeneration ◽  
Specific Expression

AbstractZebrafish are an effective model organism for retinal regeneration studies. Regenerated retinal cells are derived from Müller glia (MG) stem cells. Mammalian MG can also produce new retinal neurons; however, this regenerative potential remains dormant in the absence of genetic and/or chemical stimulation. An understanding of how the regenerative potential of MG is regulated could aid efforts to promote regeneration therapeutically. Following widespread retinal cell death, developmental signaling coordinates regeneration. Less is known about how MG respond to the loss of specific cell types, i.e., paradigms similar to retinal degenerative diseases. To address this, transcriptomic responses to the selective loss of rod photoreceptors or retinal bipolar cells were compared over twelve timepoints spanning cell degeneration and regeneration. Shared and paradigm-specific expression changes were identified throughout regeneration. Overall, paradigm-specific changes predominated, suggesting cell-specific mechanisms for activating MG stem cells. One particularly interested finding new for retinal regeneration was early regulation of SOCS family genes. These are associated with stat3 activation and the JAK/STAT pathway which has been well documented in similar studies and was further supported in our analyses. These data support the concept that selective retinal cell loss can elicit cell-specific regenerative programs and provide novel insights into retinal regeneration.

scholarly journals TUNEL Assay: A Powerful Tool for Kidney Injury Evaluation

2021 ◽  
Vol 22 (1) ◽  
pp. 412
Author(s):  
Christopher L. Moore ◽  
Alena V. Savenka ◽  
Alexei G. Basnakian
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
Cell Injury ◽  
Kidney Injury ◽  
Cell Types ◽  
Tunel Assay ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Hypoxic Injury ◽  
Additional Information ◽  
Tissue Compartments

Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay is a long-established assay used to detect cell death-associated DNA fragmentation (3’-OH DNA termini) by endonucleases. Because these enzymes are particularly active in the kidney, TUNEL is widely used to identify and quantify DNA fragmentation and cell death in cultured kidney cells and animal and human kidneys resulting from toxic or hypoxic injury. The early characterization of TUNEL as an apoptotic assay has led to numerous misinterpretations of the mechanisms of kidney cell injury. Nevertheless, TUNEL is becoming increasingly popular for kidney injury assessment because it can be used universally in cultured and tissue cells and for all mechanisms of cell death. Furthermore, it is sensitive, accurate, quantitative, easily linked to particular cells or tissue compartments, and can be combined with immunohistochemistry to allow reliable identification of cell types or likely mechanisms of cell death. Traditionally, TUNEL analysis has been limited to the presence or absence of a TUNEL signal. However, additional information on the mechanism of cell death can be obtained from the analysis of TUNEL patterns.

scholarly journals Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander Beatty ◽  
Tanu Singh ◽  
Yulia Y. Tyurina ◽  
Vladimir A. Tyurin ◽  
Svetlana Samovich ◽  
...  
Keyword(s):  
Cell Death ◽  
Therapeutic Potential ◽  
Neutral Lipids ◽  
Cell Types ◽  
Lipid Hydroperoxides ◽  
Conjugated Linolenic Acids ◽  
Cellular Lipids ◽  
Transcriptional Changes ◽  
Acyl Chains ◽  
Tumor Growth And Metastasis

AbstractFerroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

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