CXCR4 and CXCR7 Mediate TFF3-Induced Cell Migration Independently From the ERK1/2 Signaling Pathway.

Purpose: Trefoil factor family (TFF) peptides, and in particular TFF3, are characteristic secretory products of mucous epithelia that promote antiapoptosis, epithelial migration, restitution, and wound healing. For a long time, a receptor for TFF3 had not yet been identified. However, the chemokine receptor CXCR4 has been described as a low affinity receptor for TFF2.

Isolation and Investigation of Presumptive Murine Lacrimal Gland Stem Cells.

Purpose: Aqueous tear deficiency due to lacrimal gland insufficiency is one of the major causes of dry eye disease. In severe cases, such as Sjogren's syndrome, Stevens-Johnson syndrome, or ocular cicatricial pemphigoid, therapy with artificial tears is often insufficient to relieve severe discomfort, prevent progressive ocular surface disease, or enable visual rehabilitation by corneal transplantation. Cell or organ generation from stem cells, resulting in tear-like secretion, presents an option as a suitable alternative treatment.

Morphological alterations within the peripheral fixation of the iris dilator muscle in eyes with pigmentary glaucoma.

Purpose: To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG).

Methods: Using 63 control eyes (age 18 months-99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin.

Insulin-like factor 3 promotes wound healing at the ocular surface.

Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis. We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 (relaxin/insulin-like family peptide receptor 2) at the ocular surface and in tears. Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface and lacrimal apparatus; in human corneal (HCE), conjunctival (HCjE), and sebaceous (SC) epithelial cell lines; and in human tears by RT-PCR and ELISA.

Relaxin 2 is functional at the ocular surface and promotes corneal wound healing.

Purpose: We aimed to determine if the insulin-like peptide hormone relaxin 2 (RLN2) is expressed at the ocular surface and in tears and if RLN2 influences wound healing at the ocular surface, which is associated with extracellular matrix (ECM) remodeling.

Methods: We analyzed transcript levels of human RLN2 and its cognate relaxin-like receptors RXFP1 and RXFP2 in tissues of the ocular surface, lacrimal apparatus, and human corneal (HCE), conjunctival (HCjE) and sebaceous (SC) cell lines. We analyzed effects of human RLN2 on cell proliferation and migration and quantified mRNA expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in HCE, HCjE, and SC.

Comparative anatomy of the human and canine efferent tear duct system--impact of mucin MUC5AC on lacrimal drainage.

Purpose: To investigate the histomorphology of the canine tear drainage system and to show the distribution of mucin MUC5AC within the tissue.

Methods: Conjunctiva and tear drainage systems of 19 long-nosed dogs were investigated histologically and ultrastructurally. The tissues were stained with eight different antibodies reactive against less glycosylated and highly-glycosylated MUC5AC.

In vitro evidence of involvement of the epithelial y+ transporter in β-defensin production on the ocular surface.

To analyse the hypothesis as to whether there is a functional relationship between human cationic amino acid transporters (hCATs, y(+) transporter, the main transporter of L-arginine and L-lysine) and human β-defensin (important components of immune function) production on the ocular surface, arginase and nitrate monoxide synthase (NOS), enzymes that compete for L-arginine, were inhibited by norNOHA (N(omega)-hydroxy-nor-L-arginine) and/or L-NAME (NG-nitro-L-arginine methyl ester) in cultured human corneal epithelial cells. In addition, the transport activity of hCAT proteins was inhibited or activated through α-tocopherol or PMA (phorbol myristate acetate), respectively. Concentrations of the human inducible β-defensins (hBD) 2 and 3 were determined by ELISA experiments.

Expression and regulation of antimicrobial peptide psoriasin (S100A7) at the ocular surface and in the lacrimal apparatus.

Purpose: Psoriasin, originally isolated from psoriasis as an overexpressed molecule of unknown function, has recently been identified as a principal Escherichia coli-killing antimicrobial peptide of healthy skin. The purpose of this study was to investigate the expression and antimicrobial role of psoriasin at the ocular surface and in the lacrimal apparatus.

Methods: Different tissues of the lacrimal apparatus and ocular surface were systematically analyzed by means of RT-PCR, Western blot, and immunohistochemistry for their ability to express and produce psoriasin.

Trefoil factor family peptide 2 acts pro-proliferative and pro-apoptotic in the murine retina.

Although expression of trefoil factor family (TFF) peptides has been reported in the brain, nothing is known about TFF expression in the retina. The aim of this study was to test whether TFF peptides are expressed in the murine retina and have any function here. In contrast to most tissues studied, where TFF1 and TFF3 are the predominant peptides, TFF2 is the only peptide expressed in the murine retina.

Virtual microscopy-The future of teaching histology in the medical curriculum?

Conventional continuing education in microscopic anatomy, histopathology, hematology and microbiology has hitherto been carried out using numerous sets of sectioned tissue specimens in a microscopy laboratory. In comparison, after digitalization of the sections it would be possible to access teaching specimens via virtual microscopy and the internet at any time and place. This would make it possible to put innumerable new learning scenarios into practice.

Roles of human beta-defensins in innate immune defense at the ocular surface: arming and alarming corneal and conjunctival epithelial cells.

Human beta-defensins are cationic peptides produced by epithelial cells that have been proposed to be an important component of immune function at mucosal surfaces. In this study, the expression and inducibility of beta-defensins at the ocular surface were investigated in vitro and in vivo. Expression of human beta-defensins (hBD) was determined by RT-PCR and immunohistochemistry in tissues of the ocular surface and lacrimal apparatus.

Antimicrobial peptides as a major part of the innate immune defense at the ocular surface.

The ocular surface is in constant contact with the environment (e.g. when using one's fingers to insert a contact lens) and thus also with diverse bacteria, bacterial components and their pathogen associated molecules.

Cationic amino acid transporters and beta-defensins in dry eye syndrome.

Several diseases concomitant with L-arginine deficiency (diabetes, chronic kidney failure, psoriasis) are significantly associated with dry eye syndrome. One important factor that has so far been neglected is the y(+) transporter. In humans, y(+) accounts for nearly 80% of arginine transport, exclusively carrying the cationic amino acids L-arginine, L-lysine and L-ornithine.

Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye.

The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as beta-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye.

Trefoil factor 3 is induced during degenerative and inflammatory joint disease, activates matrix metalloproteinases, and enhances apoptosis of articular cartilage chondrocytes.

Objective: Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a member of a family of protease-resistant peptides containing a highly conserved motif with 6 cysteine residues. Recent studies have shown that TFF3 is expressed in injured cornea, where it plays a role in corneal wound healing, but not in healthy cornea. Since cartilage and cornea have similar matrix properties, we undertook the present study to investigate whether TFF3 could induce anabolic functions in diseased articular cartilage.

Human parotid and submandibular glands express and secrete surfactant proteins A, B, C and D.

The oral cavity and the salivary glands are open to the oral environment and are thus exposed to multiple microbiological, chemical and mechanical influences. The existence of an efficient defense system is essential to ensure healthy and physiological function of the oral cavity. Surfactant proteins play an important role in innate immunity and surface stability of fluids.

Somatostatin actions via somatostatin receptors on the ocular surface are modulated by inflammatory processes.

Recent investigations support the presence of human somatostatin (SS) in the excretory system of the human lacrimal gland. To get deeper insights into a possible role of SS at the ocular surface and in the lacrimal apparatus, we investigated the distribution pattern of SS and its receptors 1-5 (SSTR1-5) by means of RT-PCR, real-time RT-PCR, Western blot and immunodot blot analysis as well as immunohistochemistry in lacrimal gland, tear fluid, conjunctiva, cornea, nasolacrimal duct epithelium, and conjunctival (HCjE) and corneal (HCE) epithelial cell lines. Cell culture experiments with HCjE and HCE were performed to analyze a possible impact of SS and inflammatory mediators on the regulation of SSTR.

Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.

Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds.

Detection and localization of the hydrophobic surfactant proteins B and C in human tear fluid and the human lacrimal system.

Purpose: To evaluate the expression and presence of the surfactant proteins (SP) B and C in the lacrimal apparatus at the ocular surface and in tear fluid.

Methods: Expression of SP-B and SP-C was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, meibomian gland, accessory lacrimal glands, cornea, and nasolacrimal ducts. The deposition of the hydrophobic proteins SP-B and SP-C was determined by Western blot and immunohistochemistry in healthy tissues, tear fluid, and aqueous humor.

Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system.

Purpose: To evaluate the expression and presence of surfactant protein (SP) A and SP-D in the lacrimal apparatus, at the ocular surface, and in tears in healthy and pathologic states.

Methods: Expression of mRNA for SP-A and SP-D was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal ducts as well as in a spontaneously immortalized conjunctival epithelial cell line (HCjE; IOBA-NHC) and a SV40-transfected cornea epithelial cell line (HCE). Deposition of SP-A and SP-D was determined by Western blot, dot blot, and immunohistochemistry in healthy tissues, in tears, aqueous humor, and in sections of different corneal abnormalities (keratoconus, herpetic keratitis, and Staphylococcus aureus-based ulceration).

MUC16 in the lacrimal apparatus.

The aim of the present study was to determine the possible expression of the mucin MUC16 in the lacrimal apparatus. Expression and distribution of MUC16 in lacrimal gland, accessory lacrimal glands, and nasolacrimal ducts was monitored by RT-PCR and immunohistochemistry. MUC16 was expressed and detected in all tissues investigated.

Drainage of tears: impact on the ocular surface and lacrimal system.

The human efferent tear ducts are part of the lacrimal system. Because little knowledge exists concerning the physiology of the nasolacrimal system, and hence its patho- physiology, the nasolacrimal system has received almost no consideration as a possible factor in dry eye. The human nasolacrimal ducts consist of the upper and the lower lacrimal canaliculus, the lacrimal sac, and the nasolacrimal duct.

Mucins and TFF peptides of the tear film and lacrimal apparatus.

The three-dimensional organization of the tear film, which is produced and drained by the different structures of the ocular adnexa, is essential for maintainance and protection of the ocular surface. This is facilitated by a class of large, highly glycosylated, hydrophilic glycoproteins, the mucins, which are usually expressed in association with a class of peptides having a well-defined, structurally conserved trefoil domain, the mammalian trefoil factor family (TFF) peptides. In this review, the latest information regarding mucin and TFF peptide function and regulation in the human lacrimal system, the tear film and the ocular surface is summarized with regard to mucous epithelia integrity, rheological and antimicrobial properties of the tear film and tear outflow, age-related changes and certain disease states such as dry eye, dacryostenosis and dacryolith formation.

Influence of various cell-detachment solutions on endothelial cells after catheter abrasion for prosthesis colonization prior to implantation.

We (1) evaluated the effectiveness of different media on the detachment of endothelial cells (ECs) from a catheter brush (Cragg thrombolytic catheter system) that was previously used for endothelial cell abrasion in 10 cm human umbilical vein (HUV) segments; (2) tested the practicability of endovascular catheter brush abrasion followed by EC detachment from the catheter brush, in vitro culture of harvested ECs, and finally endothelialization of a prosthesis; and (3) analyzed the defect created by the catheter brush in HUV segments after endovascular catheter abrasion. Best results in detachment of ECs from the catheter brush were obtained with a mixture of phosphate-buffered saline + 1% human albumin. EC vitality was time-dependent in the collected HUV segments postdelivery.