Consequences of Preservative Uptake and Release by Contact Lenses.

Objectives: To assess contact lens preservative uptake and release from multipurpose solutions (MPS) and subsequent acquisition of lens antibacterial activity.

Methods: Kinetics of uptake and release of poly (hexamethylene biguanide hydrochloride) (PHMB) or polyquaternium-1 (PQ-1) from various contact lenses were studied initially with the pure compounds and then after soaking in MPS containing these compounds. Lenses soaked in MPS were tested for antibacterial activity.

Development of an in vitro model to study the biological effects of blinking.

Purpose: To develop a mechanical model in which a contact lens is swept over ocular surface cells under conditions that mimic the force and speed of the blink, and to investigate the resulting biological changes.

Methods: A computer controlled mechanical instrument was developed to hold a dish containing 3D cultured stratified human ocular surface epithelial cells, across which an arm bearing a contact lens was swept back and forth repeatedly at a speed and force mimicking the human blink. Cells were subjected to repeated sweep cycles for up to 1 h at a speed of 120 mm/s with or without an applied force of 19.

Effects of MMP12 on cell motility and inflammation during corneal epithelial repair.

Corneal epithelial defects are a common cause of ocular morbidity and can result in corneal scarring if they do not heal properly. Matrix metalloproteinases (MMPs) are extracellular matrix proteinases that regulate multiple aspects of corneal repair. We have previously shown that MMP12 has a protective effect on corneal fibrosis through its regulation of neutrophil and macrophage infiltration and angiogenesis in a chemical injury model involving full thickness damage to the cornea.

The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.

Corneal epithelial wound repair involves the migration of epithelial cells to cover the defect followed by the proliferation of the cells to restore thickness. Heparan sulfate proteoglycans (HSPGs) are ubiquitous extracellular molecules that bind to a plethora of growth factors, cytokines, and morphogens and thereby regulate their signaling functions. Ligand binding by HS chains depends on the pattern of four sulfation modifications, one of which is 6-O-sulfation of glucosamine (6OS).

Protective effects of matrix metalloproteinase-12 following corneal injury.

Corneal scarring due to injury is a leading cause of blindness worldwide and results from dysregulated inflammation and angiogenesis during wound healing. Here we demonstrate that the extracellular matrix metalloproteinase MMP12 (macrophage metalloelastase) is an important regulator of these repair processes. Chemical injury resulted in higher expression of the fibrotic markers α-smooth muscle actin and type I collagen, and increased levels of angiogenesis in corneas of Mmp12(-/-) mice compared with corneas of wild-type mice.

AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2.

Bacterial flagellin can interact with both Toll-like receptor 5 (TLR5) and the cell surface glycolipid, asialoGM1, to activate an innate immune response. The induction of mucin by flagellin in human lung epithelial cells (NCIH292) is dependent on asialoGM1 ligation, ATP receptor signaling, Ca2+ mobilization, and Erk1/2 activation. Conversely, the activation of NF-kappaB by flagellin is dependent on signaling through TLR5.

Adenosine up-regulation of the mucin gene, MUC2, in asthma.

Mucus hypersecretion is a hallmark of asthma that contributes to airway obstruction. While the etiology is not well understood, hypersecretion has been linked to the presence of cytokines such as IL-4, IL-5, IL-9, and IL-13 in the inflamed airway. The presence of adenosine has also been noted in asthmatic airways, and adenosine-mediated signaling in mast cells has been implicated in the severe bronchoconstriction and inflammation prevalent in these patients (1, 2).

Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins.

Invasion of epithelial cells represents a potential pathogenic mechanism for Pseudomonas aeruginosa. We explored the role of mitogen-activated protein kinase kinases (MEK 1/2) and the extracellular signal-regulated kinases (ERK 1/2) in P. aeruginosa invasion.