Corneal Infantile Myofibromatosis Caused by Novel Activating Imatinib-Responsive Variants in .

Purpose: To investigate the genetic cause, clinical characteristics, and potential therapeutic targets of infantile corneal myofibromatosis.

Design: Case series with genetic and functional analyses.

Participants: Four individuals from 2 unrelated families with clinical signs of corneal myofibromatosis were investigated.

Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma.

Angiogenesis and immune protection are essential at the onset of tumorigenesis. Angiogenesis serves to nourish the tumor, and prevention of immune defenses, for example, by dendritic cells (DCs), allows tumor growth. In this study, we investigated whether there are factors with dual functions that are both angiogenic and immunomodulatory and represent a therapeutic target.

Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3.

Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection. Endogenous regulation of lymphangiogenesis is only partly understood. Here we use the normally avascular cornea as a model to identify endogenous regulators of lymphangiogenesis.

Correlation of Clinical Fibrillar Layer Detection and Corneal Thickness in Advanced Fuchs Endothelial Corneal Dystrophy.

Central subendothelial geographic deposits are formed as a fibrillar layer (FL) in advanced Fuchs endothelial corneal dystrophy (FECD). Previous studies demonstrated a significant decrease in corneal endothelial cell (CEC) density and an increase in focal corneal backscatter in the FL area. The present study investigated the association of the FL with edema formation and its localization.

Scheimpflug Backscatter Imaging of the Fibrillar Layer in Fuchs Endothelial Corneal Dystrophy.

Unlabelled: A central collagen-rich subendothelial fibrillar layer (FL) correlates with areas of accentuated loss of corneal endothelial cells in advanced Fuchs endothelial corneal dystrophy (FECD). The present study sought to investigate whether the FL may be visualized by en face Scheimpflug backscatter imaging in vivo.

Design: Retrospective analysis of a prospective observational case series.

MAdCAM-1/α4β7 Integrin-Mediated Lymphocyte/Endothelium Interactions Exacerbate Acute Immune-Mediated Hepatitis in Mice.

Background & Aims: Aberrant lymphocyte homing could potentially link inflammatory processes in the intestine and the liver, as distinct hepatobiliary diseases frequently develop as extra-intestinal manifestations in inflammatory bowel disease. In this study, we examined the role of the gut-tropic leukocyte adhesion molecule β7 integrin and its endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) in immune-mediated hepatitis in mice.

Methods: Wild-type (WT) mice, MAdCAM-1-deficient mice, β7 integrin-deficient mice, RAG-2-deficient mice, RAG-2/MAdCAM-1 double-deficient mice, and RAG-2/β7 integrin double-deficient mice were subjected to concanavalin A (ConA)-induced hepatitis.

Fibrillar Layer as a Marker for Areas of Pronounced Corneal Endothelial Cell Loss in Advanced Fuchs Endothelial Corneal Dystrophy.

Purpose: We sought to assess the correlation of corneal endothelial cell (CEC) density to alterations of collagen composition of Descemet membrane (DM) in advanced Fuchs endothelial corneal dystrophy (FECD) and to image such changes by slit-lamp biomicroscopy in vivo.

Design: Prospective, observational consecutive case series.

Methods: Fifty eyes (50 subjects) with advanced FECD were enrolled.

Effect of Iris Color on the Outcome of Descemet Membrane Endothelial Keratoplasty.

Purpose: To explore the impact of iris color on the outcome of Descemet membrane endothelial keratoplasty (DMEK).

Methods: Consecutive cases of Fuchs endothelial dystrophy after DMEK were retrospectively analyzed from the prospective Cologne DMEK database between 2011 and 2017 at the University of Cologne, Germany. Iris pictures were graded by color into blue, green, or brown and compared regarding outcome parameters including best-corrected visual acuity (converted to logarithm of the minimal angle of resolution), central corneal thickness, endothelial cell density (ECD), each at preoperative (baseline) and postoperative 12 months, rebubbling rates, cystoid macular edema (CME), and immune rejections after surgery.

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation.

Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation.

Bevacizumab Induces Upregulation of Keratin 3 and VEGFA in Human Limbal Epithelial Cells in Vitro.

Topical application of vascular endothelial growth factor A (VEGFA) inhibitors including Bevacizumab is used for antiangiogenic therapy at the ocular surface. While clinical studies have suggested that this approach is well-tolerated, the effect of the drug on limbal epithelial stem cells has not been studied. In this study, the effect of Bevacizumab on phenotype and functionality of putative limbal epithelial stem cells (SC) was investigated.

Fuchs Endothelial Corneal Dystrophy: Clinical, Genetic, Pathophysiologic, and Therapeutic Aspects.

Fuchs endothelial corneal dystrophy (FECD) is a bilateral corneal endothelial disorder and the most common cause of corneal transplantation worldwide. Professor Ernst Fuchs described the first 13 cases of FECD more than 100 years ago. Since then, we have seen far-reaching progress in its diagnosis and treatment.

Tyrosinase Is a Novel Endogenous Regulator of Developmental and Inflammatory Lymphangiogenesis.

Lymphangiogenesis is critically involved in tissue fluid balance, graft rejection, and tumor metastasis. Endogenous regulation of lymphangiogenesis is poorly understood. Herein, we use the lymphatic vessel architecture at the limbal border of the normally avascular cornea, a quantitative trait under strong genetic influence, as a model system to identify new candidate genes regulating lymphangiogenesis.

Notch inhibition counteracts Paneth cell death in absence of caspase-8.

Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity.

Photodynamic Therapy Leads to Time-Dependent Regression of Pathologic Corneal (Lymph) Angiogenesis and Promotes High-Risk Corneal Allograft Survival.

Purpose: Pathologic corneal (lymph) angiogenesis is a known risk factor for immune-mediated allograft rejections after corneal transplantation. However, there is no established treatment to regress pre-existing pathological corneal blood and lymphatic vessels. This study assessed the possibility to regress both vessel types by photodynamic therapy (PDT) after intravenous (i.

[New Therapeutic Approaches in Inflammatory Diseases of the Eye - Targeting Lymphangiogenesis and Cellular Immunity: Research Unit FOR 2240 Presents Itself].

Ophthalmology, principally, is a very successful subdiscipline in medicine. Nonetheless, there are still unmet medical needs which necessitate translational research. The funding instrument of a Research Unit (RU) of the German Research Foundation (DFG) is presented as exemplified by the RU 2240 at the Department of Ophthalmology at the University of Cologne.

β-Integrin and MAdCAM-1 play opposing roles during the development of non-alcoholic steatohepatitis.

Background & Aims: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. It is unclear how infiltrating leukocytes affect NASH-development. Our study aims to investigate the role of the homing/receptor, pair mucosal addressin cell adhesion molecule-1 (MAdCAM-1)/β-Integrin, on immune cell recruitment and disease progression in a steatohepatitis model.

β7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon.

Leukocyte recruitment is pivotal for the initiation and perpetuation of inflammatory bowel disease (IBD) and controlled by the specificity and interactions of chemokines and adhesion molecules. Interactions of the adhesion molecules α4β7-integrin and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) promote the accumulation of pathogenic T-cell populations in the inflamed intestine. We aimed to elucidate the significance of β7-integrin expression on innate immune cells for the pathogenesis of IBD.

Beta-7 integrin controls enterocyte migration in the small intestine.

Aim: To hypothesize that beta-7 integrin affects cellular migration of both, lymphocytes and enterocytes.

Methods: The nucleoside analog BrdU was ip injected in beta-7-deficient mice (C57BL/6-Itgb(tmlcgn)/J) of male gender and age-matched male C57BL/J J mice (wild type) 4, 20, or 40 h before analysis. The total small intestine was isolated, dissected, and used for morphometrical studies.

Localization of dendritic cells in the gut epithelium requires MAdCAM-1.

Directed migration of immune cells is a prerequisite for immune responses. T and B cell migration to the gut is secured by interaction of mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) and β7 integrin. Here we report a novel function for MAdCAM-1: that of mediating intestinal localization of dendritic cells (DCs).

β7 integrin controls immunogenic and tolerogenic mucosal B cell responses.

IgA production in the gut-associated lymphoid tissue represents a pivotal defense mechanism against luminal pathogens. The other important challenge for the GALT is the induction of local and systemic hyporesponsiveness (tolerance) to dietary antigens and luminal bacterial flora to prevent allergies or deleterious immunologic reactions to food or environmental antigens. In this study we analyzed the impact of β7 integrin on immunogenic and tolerogenic B cell responses in the gastrointestinal tract.

Interleukin-6 acts in the fashion of a classical chemokine on monocytic cells by inducing integrin activation, cell adhesion, actin polymerization, chemotaxis, and transmigration.

Macrophages contribute to the innate immune response by eliminating bacteria, viral particles, and apoptotic bodies. They develop from circulating monocytes. In case of an infection, monocytes attach to the endothelial cells of the blood vessels, migrate along the endothelial cells, leave the circulatory system to enter the inflammatory tissue, and differentiate into macrophages.