Pax6 induces ectopic eyes in a vertebrate

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4213-4222 ◽  
Author(s):  
R.L. Chow ◽  
C.R. Altmann ◽  
R.A. Lang ◽  
A. Hemmati-Brivanlou
Keyword(s):  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ectopic Expression ◽  
Spatial Arrangement ◽  
Lineage Tracing ◽  
Dominant Negative ◽  
Retinal Pigment Epithelial Cells ◽  
Dominant Negative Form ◽  
Ectopic Eyes

We report here that misexpression of the transcription factor Pax6 in the vertebrate Xenopus laevis leads to the formation of differentiated ectopic eyes. Multiple molecular markers indicated the presence of mature lens fiber cells, ganglion cells, Muller cells, photoreceptors and retinal pigment epithelial cells in a spatial arrangement similar to that of endogenous eyes. Lineage tracing experiments showed that lens, retina and retinal pigment epithelium arose as a consequence of the cell-autonomous function of Pax6. These experiments also reveal that the cell autonomous activity of misexpressed Pax6 causes the ectopic expression of a number of genes including Rx, Otx2, Six3 and endogenous Pax6, each of which has been implicated in eye development. The formation of ectopic and endogenous eyes could be suppressed by coexpression of a dominant-negative form of Pax6. These data show that in vertebrates, as in the invertebrate Drosophila melanogaster, Pax6 is both necessary and sufficient to trigger the cascade of events required for eye formation.

Pigment Epithelium-Derived Factor: A Novel Therapeutic Target for Cardiometabolic Diseases and Related Complications

2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui
Keyword(s):  
Cardiovascular Disease ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visceral Obesity ◽  
Retinal Pigment Epithelial Cells ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
Pigment Epithelium Derived Factor ◽  
Cardiometabolic Disorders

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.

scholarly journals A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 179
Author(s):  
Laurence Klipfel ◽  
Marie Cordonnier ◽  
Léa Thiébault ◽  
Emmanuelle Clérin ◽  
Frédéric Blond ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Lactate Transport ◽  
Ips Cell ◽  
Risk Alleles ◽  
Age Related ◽  
A Genome

Age-related macular degeneration (AMD) is a blinding disease for which most of the patients remain untreatable. Since the disease affects the macula at the center of the retina, a structure specific to the primate lineage, rodent models to study the pathophysiology of AMD and to develop therapies are very limited. Consequently, our understanding relies mostly on genetic studies highlighting risk alleles at many loci. We are studying the possible implication of a metabolic imbalance associated with risk alleles within the SLC16A8 gene that encodes for a retinal pigment epithelium (RPE)-specific lactate transporter MCT3 and its consequences for vision. As a first approach, we report here the deficit in transepithelial lactate transport of a rare SLC16A8 allele identified during a genome-wide association study. We produced induced pluripotent stem cells (iPSCs) from the unique patient in our cohort that carries two copies of this allele. After in vitro differentiation of the iPSCs into RPE cells and their characterization, we demonstrate that the rare allele results in the retention of intron 2 of the SLC16A8 gene leading to the absence of MCT3 protein. We show using a biochemical assay that these cells have a deficit in transepithelial lactate transport.

scholarly journals Expression of pigment epithelium-derived factor and thrombospondin-1 regulate proliferation and migration of retinal pigment epithelial cells

2015 ◽  
Vol 3 (1) ◽  
pp. e12266 ◽  
Author(s):  
Mitra Farnoodian ◽  
James B. Kinter ◽  
Saeed Yadranji Aghdam ◽  
Ismail Zaitoun ◽  
Christine M. Sorenson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelium Derived Factor ◽  
And Migration ◽  
Pigment Epithelial Cells ◽  
Proliferation And Migration

Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV

2018 ◽  
Vol 117 ◽  
pp. 238-246 ◽  
Author(s):  
Chun-zhou Tang ◽  
Ke-Ran Li ◽  
Qing Yu ◽  
Qin Jiang ◽  
Jin Yao ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Ganglion ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

Wingless blocks bristle formation and morphogenetic furrow progression in the eye through repression of Daughterless

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3393-3402 ◽  
Author(s):  
Kenneth M. Cadigan ◽  
Austin D. Jou ◽  
Roel Nusse
Keyword(s):  
Gene Expression ◽  
Ectopic Expression ◽  
Dominant Negative ◽  
Proneural Gene ◽  
Morphogenetic Furrow ◽  
Heterologous Promoter ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Dominant Negative Form ◽  
Negative Form

In the developing eye, wingless activity represses proneural gene expression (and thus interommatidial bristle formation) and positions the morphogenetic furrow by blocking its initiation in the dorsal and ventral regions of the presumptive eye. We provide evidence that wingless mediates both effects, at least in part, through repression of the basic helix-loop-helix protein Daughterless. daughterless is required for high proneural gene expression and furrow progression. Ectopic expression of wingless blocks Daughterless expression in the proneural clusters. This repression, and that of furrow progression, can be mimicked by an activated form of armadillo and blocked by a dominant negative form of pangolin/TCF. Placing daughterless under the control of a heterologous promoter blocks the ability of ectopic wingless to inhibit bristle formation and furrow progression. hedgehog and decapentapleigic could not rescue the wingless furrow progression block, indicating that wingless acts downstream of these genes. In contrast, Atonal and Scute, which are thought to heterodimerize with Daughterless to promote furrow progression and bristle formation, respectively, can block ectopic wingless action. These results are summarized in a model where daughterless is a major, but probably not the only, target of wingless action in the eye.

Non-random spatial arrangement of clone sizes in chimaeric retinal pigment epithelium

Development ◽  
1986 ◽  
Vol 91 (1) ◽  
pp. 197-208
Author(s):  
Günter H. Schmidt ◽  
Maureen M. Wilkinson ◽  
Bruce A. J. Ponder
Keyword(s):  
Retinal Pigment Epithelium ◽  
Patch Size ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Spatial Arrangement ◽  
Tissue Growth ◽  
Geometric Means ◽  
Frequency Distributions ◽  
Size Frequency ◽  
Wide Range

Clonal analysis of whole-mount preparations of entire retinal pigment epithelium (RPE), using SWR ↔ C57BL/6JLac and DDK ↔ C3H/Bi mouse aggregation chimaeras in which one of the two parental components predominated, revealed a markedly non-random spatial arrangement of patch (clone) sizes. Single-cell and small patches predominated in an area around the optic nerve head while large patches occurred most frequently near the periphery. Mechanisms are discussed which may explain these results. Patch size frequency distributions were concave and skewed. Singletons were the most frequent size class, but a wide range of sizes and a smaller number of much larger patches were also always found. The results preclude the use of statistical methods previously employed to calculate clone sizes from the geometric means of observed patch sizes. Instead, the median and interquartile range may provide the best summary of the observed patch size frequency distributions. Our findings support a stochastic model of tissue growth.

The role of bone morphogenetic proteins in the differentiation of the ventral optic cup

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3161-3171 ◽  
Author(s):  
Ruben Adler ◽  
Teri L. Belecky-Adams
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ectopic Expression ◽  
Neural Retina ◽  
Optic Disk ◽  
Loss Of Function ◽  
In Ovo ◽  
Optic Stalk ◽  
Optic Cup

The ventral region of the chick embryo optic cup undergoes a complex process of differentiation leading to the formation of four different structures: the neural retina, the retinal pigment epithelium (RPE), the optic disk/optic stalk, and the pecten oculi. Signaling molecules such as retinoic acid and sonic hedgehog have been implicated in the regulation of these phenomena. We have now investigated whether the bone morphogenetic proteins (BMPs) also regulate ventral optic cup development. Loss-of-function experiments were carried out in chick embryos in ovo, by intraocular overexpression of noggin, a protein that binds several BMPs and prevents their interactions with their cognate cell surface receptors. At optic vesicle stages of development, this treatment resulted in microphthalmia with concomitant disruption of the developing neural retina, RPE and lens. At optic cup stages, however, noggin overexpression caused colobomas, pecten agenesis, replacement of the ventral RPE by neuroepithelium-like tissue, and ectopic expression of optic stalk markers in the region of the ventral retina and RPE. This was frequently accompanied by abnormal growth of ganglion cell axons, which failed to enter the optic nerve. The data suggest that endogenous BMPs have significant effects on the development of ventral optic cup structures.

scholarly journals Characterization of artificially re-pigmented ARPE-19 retinal pigment epithelial cell model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Laura Hellinen ◽  
Marja Hagström ◽  
Heidi Knuutila ◽  
Marika Ruponen ◽  
Arto Urtti ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Epithelial Cell ◽  
Cell Line ◽  
Retinal Pigment Epithelial ◽  
Cell Model ◽  
Retinal Pigment Epithelial Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial

Abstract Melanin pigment has a significant role in ocular pharmacokinetics, because many drugs bind at high extent to melanin in the retinal pigment epithelial cells. Most retinal pigment epithelial cell lines lack pigmentation and, therefore, we re-pigmented human ARPE-19 cells to generate a pigmented cell model. Melanosomes from porcine retinal pigment epithelium were isolated and co-incubated with ARPE-19 cells that spontaneously phagocytosed the melanosomes. Internalized melanosomes were functionally integrated to the cellular system as evidenced by correct translocation of cellular Rab27a protein to the melanosomal membranes. The pigmentation was retained during cell cultivation and the level of pigmentation can be controlled by altering the amount of administered melanosomes. We used these cells to study melanosomal uptake of six drugs. The uptake was negligible with low melanin-binders (methotrexate, diclofenac) whereas most of the high melanin-binders (propranolol, chloroquine) were extensively taken up by the melanosomes. This cell line can be used to model pigmentation of the retinal pigment epithelium, while maintaining the beneficial cell line characteristics, such as fast generation of cultures, low cost, long-term maintenance and good reproducibility. The model enables studies at normal and decreased levels of pigmentation to model different retinal conditions.

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