scholarly journals Targeted Overexpression of TGF-α in the Corneal Epithelium of Adult Transgenic Mice Induces Changes in Anterior Segment Morphology and Activates Noncanonical Wnt Signaling

2013 ◽  
Vol 54 (3) ◽  
pp. 1829 ◽  
Author(s):  
Yong Yuan ◽  
Lung-Kun Yeh ◽  
Hongshan Liu ◽  
Osamu Yamanaka ◽  
William D. Hardie ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Wnt Signaling ◽  
Corneal Epithelium ◽  
Anterior Segment

Formation of corneal endothelium is essential for anterior segment development - a transgenic mouse model of anterior segment dysgenesis

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 533-542
Author(s):  
L.W. Reneker ◽  
D.W. Silversides ◽  
L. Xu ◽  
P.A. Overbeek
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Corneal Epithelium ◽  
Corneal Endothelium ◽  
Transforming Growth Factor ◽  
Anterior Segment ◽  
Corneal Stroma ◽  
Corneal Opacity ◽  
Cell Types ◽  
Surface Ectoderm

The anterior segment of the vertebrate eye is constructed by proper spatial development of cells derived from the surface ectoderm, which become corneal epithelium and lens, neuroectoderm (posterior iris and ciliary body) and cranial neural crest (corneal stroma, corneal endothelium and anterior iris). Although coordinated interactions between these different cell types are presumed to be essential for proper spatial positioning and differentiation, the requisite intercellular signals remain undefined. We have generated transgenic mice that express either transforming growth factor (alpha) (TGF(alpha)) or epidermal growth factor (EGF) in the ocular lens using the mouse (alpha)A-crystallin promoter. Expression of either growth factor alters the normal developmental fate of the innermost corneal mesenchymal cells so that these cells often fail to differentiate into corneal endothelial cells. Both sets of transgenic mice subsequently manifest multiple anterior segment defects, including attachment of the iris and lens to the cornea, a reduction in the thickness of the corneal epithelium, corneal opacity, and modest disorganization in the corneal stroma. Our data suggest that formation of a corneal endothelium during early ocular morphogenesis is required to prevent attachment of the lens and iris to the corneal stroma, therefore permitting the normal formation of the anterior segment.

scholarly journals Disruption of anterior segment development by TGF-β1 overexpression in the eyes of transgenic mice

2002 ◽  
Vol 225 (2) ◽  
pp. 111-125 ◽  
Author(s):  
Cassandra Flügel-Koch ◽  
Andreas Ohlmann ◽  
Joram Piatigorsky ◽  
Ernst R. Tamm
Keyword(s):  
Transgenic Mice ◽  
Anterior Segment ◽  
Tgf Β1

scholarly journals Characterisation of the prereceptor regulation of glucocorticoids in the anterior segment of the rabbit eye

2006 ◽  
Vol 190 (2) ◽  
pp. 483-493 ◽  
Author(s):  
Claire U Onyimba ◽  
Neelima Vijapurapu ◽  
S John Curnow ◽  
Pamela Khosla ◽  
Paul M Stewart ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Corneal Epithelium ◽  
Ciliary Body ◽  
Primary Cultures ◽  
Anterior Segment ◽  
Body Tissue ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
Rabbit Eye

The prereceptor regulation of glucocorticoids (GCs) by 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a bidirectional isozyme that interconverts active (cortisol) and inactive (cortisone) GCs, is an established determinant of GC function in tissues such as liver, adipose and bone. Although the therapeutic use of GCs is abundant in ophthalmic practice, where GC interactions with nuclear receptors modulate gene transcription, the prereceptor regulation of endogenous cortisol is not well described in ocular tissues. Recent descriptive studies have localised 11β-HSD1 to the human corneal epithelium and non-pigmented epithelium (NPE) of the ciliary body, indicating a link to corneal epithelial physiology and aqueous humour production. In this study, we characterise the functional aspects of the autocrine regulation of GCs in the anterior segment of the rabbit eye. Using our in-house generated primary antibody to human 11β-HSD1, immunohistochemical analyses were performed on paraffin-embedded sections of whole New Zealand white albino rabbits, (NZWAR) eyes. As in human studies, 11β-HSD1 was localised to the corneal epithelium and the NPE. No staining was seen in the albino ‘pigmented’ ciliary epithelium. Specific enzyme assays for oxo-reductase (cortisone→cortisol) and dehydrogenase (cortisol→cortisone) activity indicated predominant 11β-HSD1 oxo-reductase activity from both the intact ciliary body tissue (n=12, median 2.1 pmol/mg per h and range 1.25–2.8 pmol/mg per h; P=0.006) and primary cultures of corneal epithelial cells (n=12, median 3.0 pmol/mg per h and range 1.0–7.4 pmol/mg per h, P=0.008) compared with dehydrogenase activity (median 1.0 pmol/mg per h and range 0.5–2.0 pmol/mg per h; median 0.5 pmol/mg per h and range 0.25–1.9 pmol/mg per h respectively). These findings were supported by expression of 11β-HSD1 protein as visualised by Western blotting of ciliary body tissue and immunocytochemistry of corneal epithelial cells. Reduction of corneal epithelial cell proliferation was seen after primary cultures were co-incubated with cortisol and cortisone. 11β-HSD1 activity was not demonstrated in naïve conjunctival fibroblasts or corneal stromal keratocytes. Our results indicate that the distribution of 11β-HSD1 in the rabbit resembles that of the human eye and activates cortisone to cortisol in both corneal and uveal tissues. The NZWAR provides a suitable in vivo model for the further evaluation of 11β-HSD1 activity in the eye, especially its role in corneal epithelial and ciliary body physiology.

scholarly journals Wnt Signaling Alteration in the Spinal Cord of Amyotrophic Lateral Sclerosis Transgenic Mice: Special Focus on Frizzled-5 Cellular Expression Pattern

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155867 ◽  
Author(s):  
Carlos González-Fernández ◽  
Renzo Mancuso ◽  
Jaume del Valle ◽  
Xavier Navarro ◽  
Francisco Javier Rodríguez
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Transgenic Mice ◽  
Wnt Signaling ◽  
Expression Pattern ◽  
Special Focus ◽  
Cellular Expression ◽  
Lateral Sclerosis

scholarly journals Klotho protects against mouse renal fibrosis by inhibiting Wnt signaling

2012 ◽  
Vol 303 (12) ◽  
pp. F1641-F1651 ◽  
Author(s):  
Minoru Satoh ◽  
Hajime Nagasu ◽  
Yoshitaka Morita ◽  
Terry P. Yamaguchi ◽  
Yashpal S. Kanwar ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Wnt Signaling ◽  
Renal Fibrosis ◽  
Negative Regulator ◽  
Mutant Mice ◽  
Tubulointerstitial Fibrosis ◽  
Soluble Form ◽  
Obstructive Nephropathy ◽  
Wild Type ◽  
Matrix Deposition

Augmented Wnt signaling has been implicated in many fibrotic diseases including obstructive nephropathy. Soluble form Klotho has been reported to function as a secreted Wnt antagonist. In this study, we tested whether Klotho protein could reduce renal fibrosis by inhibition of Wnt signaling. Transgenic mice that overexpressed Klotho, wild-type mice, and Klotho hetero mutant mice underwent unilateral ureteral obstruction (UUO). In some Klotho hetero mutant mice, Klotho-encoding plasmid was transferred into the skeletal muscle by electroporation. UUO induced activation of Wnt signaling in wild-type but less in Klotho transgenic mice. Enhanced tubulointerstitial fibrosis in wild-type mice was also attenuated in Klotho transgenic mice. In contrast, Wnt signaling and concomitant tubulointerstitial fibrosis were further augmented in Klotho hetero mutant mice after UUO compared with wild-type mice. In Klotho-encoding plasmid-transfected Klotho hetero mutant mice, however, Wnt signaling was markedly reduced accompanied by a decrease in extracellular matrix deposition after UUO. In vitro studies showed that stimulation of Wnt3a induced prolonged cell cycle arrest at G2/M phase, with a resultant increase in production of fibrogenic cytokines. Cotreatment with Klotho bypassed the G2/M arrest and reduced fibrogenic cytokine production. In conclusion, Klotho is a critical negative regulator of Wnt signaling and a suppressor of renal fibrosis in the obstructed kidney model.

scholarly journals Assessment of Corneal Epithelial Thickness in Chronic Contact Lens Users Using Anterior Segment Optical Coherence Tomography

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A M E A Rezk ◽  
A Assaf ◽  
M Gamil ◽  
T Badran
Keyword(s):  
Contact Lens ◽  
Corneal Epithelium ◽  
Refractive Surgery ◽  
Anterior Segment ◽  
Control Group ◽  
Soft Contact ◽  
Corneal Epithelial ◽  
Epithelial Thickness ◽  
Soft Contact Lens ◽  
Corneal Epithelial Thickness

Abstract Introduction The corneal epithelium is stratified epithelium that is continuously renewed and provides the frontline of defence against invading ocular pathogens and a smooth refractive surface essential for vision. In the absence of a contact lens, pre-existing ocular trauma or disease, the epithelium maintains an inaccessible defence against attacks from pathogenic microorganisms, affording a high level of resistance against microbial invasion. Aim The aim of this study is to determine the effect of chronic use of contact lens on corneal epithelium thickness using anterior segment optical coherence topography as a non- invasive diagnostic accurate measure. Patients and Methods 30 eyes of control subjects who don’t wear contact lens along their life aged between 15-45 years ,where compared with similar age group of 30 eyes of chronic contact lens users; who wear contact lens every day not less than 8 hours per day for along time interval between 6 months up to 5 years. Results The average corneal epithelial thickness in the central, paracentral and midperipheral zones was 47.767 ± 5.550 µm, 46.267 ± 5.644 µm, 44.300 ± 4.858 µm, respectively, in chronic soft contact lens users; and 49.800 ± 3.316 µm, 49.200 ± 3.367 µm, 45.733 ± 2.333 µm ,in control group who had never worn contact lens. There were insignificant thinning of corneal epithelium of soft contact group compared to control group regarding the average corneal epithelial thickness in those 3 zones. In all the 8 sectors of corneal epithelium of paracentral zone and midperipheral zones there is insignificant thinning between the two groups except for the inferior temporal sector in the paracentral zone and mid peripheral zone, which shows significant thinning in soft contact lens group compared to control group. The corneal epithelial thickness in the inferior temporal sector of paracentral and mid peripheral zones was 46.333 ± 5.677 µm, 44.933 ± 4.813 µm, respectively, in chronic soft contact lens users compared to 48.767 ± 3.266 µm, 46.900 ± 2.510 µm in control group (p = 0.046, p = 0.052, respectively). Conclusion AS-OCT helps us to evaluate the corneal epithelium of contact lens users, which could be very useful in corneal refractive surgeries in patients depending on contact lens in their lives as a comfortable refractive aid, It is necessary to do AS-OCT hand on hand with pentacam in patients underwhelming refractive surgery to give a proper assessment to their corneal epithelium before determining which type of refractive surgery suits them.

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