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.

[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.

IL-10 Indirectly Regulates Corneal Lymphangiogenesis and Resolution of Inflammation via Macrophages.

The role of IL-10, a primarily anti-inflammatory cytokine, in the regulation of inflammatory lymphangiogenesis is undetermined. Herein, we show that IL-10 modulates corneal lymphangiogenesis and resolution of inflammation. IL-10 was not expressed in healthy corneas but was up-regulated in inflamed corneas by infiltrating macrophages.

The Naïve Murine Cornea as a Model System to Identify Novel Endogenous Regulators of Lymphangiogenesis: TRAIL and rtPA.

Background: In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth.

Methods And Results: Pathway specific expression analysis of the cornea was performed to identify novel candidate genes.

Consensus statement on the immunohistochemical detection of ocular lymphatic vessels.

There is currently considerable controversy about existence and classification of "lymphatic vessels" in the eye. Some of the confusion is certainly caused by inappropriate use (or nonuse) of the correct immunohistochemical markers. Many experts in the field expressed the need for a consensus statement, and, in this perspective, authors offer arguments and solutions to reliably continue with immunohistochemical ocular lymphatic research.

Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sjögren's syndrome.

Lacrimal gland inflammation during autoimmune Sjögren's syndrome (SS) leads to ocular surface inflammation - Keratoconjunctivitis sicca (KCS). This condition afflicts both the cornea and conjunctiva that form the ocular surface. Thrombospondin-1 (TSP-1) deficiency in mice results in lacrimal gland and corneal inflammation that resembles the human disease.

Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases.

The cornea is one of the few tissues which actively maintain an avascular state, i.e. the absence of blood and lymphatic vessels (corneal [lymph]angiogenic privilege).

Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1.

LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) is a homolog of the hyaluronan receptor CD44, and one of the most widely used markers of lymphatic endothelial cells in normal and tumor tissues. However, the physiologic role of LYVE-1 in the lymphatic system still remains unclear. It is well established that fibroblast growth factor 2 (FGF2) induces lymphangiogenesis.

Topical Ranibizumab inhibits inflammatory corneal hem- and lymphangiogenesis.

Purpose: Ranibizumab (Lucentis(®) ) is a Fab-Fragment of a recombinant, humanized, monoclonal VEGF (anti-vascular endothelial growth factor) antibody. This study analyzed the ability of topical Ranibizumab to inhibit lymphangiogenesis in addition to hemangiogenesis after acute corneal inflammation in vivo. In addition, the effect of Ranibizumab on the proliferation of human lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) in vitro was studied.

Corneal angiogenesis and lymphangiogenesis.

Purpose Of Review: The purpose of the present review is to describe new antilymphangiogenic treatment strategies and recent findings on strain-dependency of corneal lymphangiogenesis and the interdependency between blood and lymphatic vessel growth.

Recent Findings: Studies on mice have revealed that apart from haemangiogenesis, lymphangiogenesis can also differ markedly between several mouse strains under normal and inflammatory conditions. Although haemangiogenesis and lymphangiogenesis are closely interconnected in their spatial-temporal patterning, recent data suggest that they can also occur independently.

Blockade of insulin receptor substrate-1 inhibits corneal lymphangiogenesis.

Purpose: To analyze whether insulin receptor substrate (IRS-1) is involved in lymphatic vessel development and whether IRS-1 blockade can inhibit lymphangiogenesis in vivo.

Methods: The impact of IRS-1 blockade by GS-101 (Aganirsen), an antisense oligonucleotide against IRS-1, on lymphatic endothelial cell (LEC) proliferation was assessed by ELISA. Furthermore, the effect of IRS-1 blockade on prolymphangiogenic growth factor expression by LECs and macrophages (peritoneal exudate cells) was tested by real-time PCR.

Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids.

Objectives: To analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis and to study the potential underlying antilymphangiogenic mechanisms.

Methods: Inflammatory corneal neovascularization was induced by suture placement, and the corneas were then treated with topical fluorometholone, prednisolone acetate, or dexamethasone sodium phosphate. After 1 week, the corneas were stained with lymphatic vessel endothelial hyaluronan receptor 1 for detection of pathological corneal lymphangiogenesis.

Genetic heterogeneity of lymphangiogenesis in different mouse strains.

Lymphangiogenesis plays an important role in tumor metastasis, wound healing, and immune reactions, such as after organ transplantation. Furthermore, novel antilymphangiogenic drugs are moving into clinical medicine, but so far nothing is known about a potential genetic heterogeneity influencing lymphangiogenesis. Using the mouse cornea micropocket assay (VEGF-C) and the suture-induced corneal neovascularization model in different inbred and wild-derived mouse strains (Balb/cAnNCrl, C57BL/6NCrl, 129S1/SvImJ, SJL/JCrl, Cast/EiJ, FVB/NCrl), significant differences in the lymphangiogenic response were detected: the lymphvascularized area varied up to 1.

Corneal (lymph)angiogenesis--from bedside to bench and back: a tribute to Judah Folkman.

The normal cornea, the transparent "windscreen" of the eye, is devoid of both blood and lymphatic vessels. Nevertheless, both hem- and lymphangiogenesis can occur in response to severe corneal inflammation and can lead to blindness. Judah Folkman and co-workers exceedingly used the normally avascular cornea as the in vivo model system to study the mechanisms of angiogenesis and to test activators and inhibitors of angiogenesis in the last 3 decades.