In vitro and in vivo comparative toxicological study of a new preservative-free latanoprost formulation.

Purpose: To compare in vitro, on the human reconstituted corneal epithelial SkinEthics model, and in vivo, using an acute rabbit toxicological model, the effects of a benzalkonium chloride (BAK)-preserved solution of latanoprost and a preservative-free (PF) latanoprost solution.

Methods: In vitro, the three-dimensional (3D) reconstituted human corneal epithelia (HCE) were treated with PBS, BAK-latanoprost, PF-latanoprost, or 0.02% BAK for 24 hours followed or not followed by a 24 hour post incubation recovery period.

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system.

Aims: Using an established three-dimensional (3D) toxicological model based on reconstituted human corneal epithelium (HCE), this study investigated the tolerability of four topical intraocular-pressure-lowering agents: the commercial solutions of benzalkonium chloride (BAC)-containing 0.005% latanoprost, 0.004% travoprost, 0.

Polyquad-preserved travoprost/timolol, benzalkonium chloride (BAK)-preserved travoprost/timolol, and latanoprost/timolol in fixed combinations: a rabbit ocular surface study.

Introduction: The aim of this study was to use a validated acute rabbit model to test the toxicity of a novel formulation of fixed-combination travoprost 0.004%/timolol 0.5% ophthalmic solution, which contains the antimicrobial preservative polyquaternium-1 (PQ), compared with the commercial formulation of fixed combinations travoprost 0.

Preservatives in eyedrops: the good, the bad and the ugly.

There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.

Occludin gene expression as an early in vitro sign for mild eye irritation assessment.

Purpose: To test a new multiple endpoint analysis (MEA) including occludin gene expression for screening the ocular irritation potential of tear substitutes on human corneal epithelium (HCE), an in vitro model proposed to limit the use of animal testing in pre-clinical studies.

Methods: Four chemically-preserved and two non chemically-preserved tear substitutes were tested after acute (24h, 24h+24h post incubation) and repeated applications (for 72h) and compared to the positive control, benzalkonium chloride (BAK) at 0.1% and 0.

Multiple endpoint analysis of the 3D-reconstituted corneal epithelium after treatment with benzalkonium chloride: early detection of toxic damage.

Purpose: To investigate the effects of benzalkonium chloride (BAK) on the human reconstituted corneal epithelial model (HCE) and to optimize the operating potential of this model in the field of ophthalmic toxicology.

Methods: The HCEs were treated with 0.001% to 0.

Th1- and Th2-related chemokine and chemokine receptor expression on the ocular surface in endotoxin-induced uveitis.

Purpose: To determine whether the ocular surface inflammation in uveitis mimics or counteracts intraocular inflammatory pathways by directly comparing T-helper (Th) lymphocytes Th1 and Th2 markers in conjunctival and ciliary body expression in endotoxin-induced uveitis (EIU). This study used the following inflammatory markers: chemokine receptor, CC chemokine receptor 4 (CCR4), and its ligand, macrophage-derived chemokine (MDC), to evaluate Th2 participation; chemokine receptor, CCR5, to evaluate the Th1 system; and its ligand, regulated on activation normal T cell expressed and secreted (RANTES), to evaluate both Th1 and Th2 systems.

Methods: Immunohistochemistry and real-time polymerase chain reaction (RT-PCR) were used to compare protein and RNA expression of CCR4, MDC, CCR5, and RANTES in the conjunctiva and ciliary body in EIU 6 h and 24 h after the lipopolysaccharide (LPS) injection and in control (without injection) Lewis rats.

In vivo confocal microscopic grading system for standardized corneal evaluation: application to toxic-induced damage in rat.

Purpose: To propose an in vivo confocal microscopic scoring system for evaluation of irritant-induced corneal changes.

Materials And Methods: Rat corneas were instilled with 0.01-0.

New tools for the evaluation of toxic ocular surface changes in the rat.

Purpose: To assess the usefulness of noninvasive combined technologies used to observe ocular surface changes in toxicology studies.

Methods: Benzalkonium chloride (BAC) at 0.01%, 0.

LPS-stimulated inflammation and apoptosis in corneal injury models.

Purpose: To evaluate and compare the proinflammatory and apoptotic effects of lipopolysaccharide (LPS) in three rabbit corneal injury models using a new in vivo confocal microscope (IVCM) and immunohistological techniques.

Methods: Adult male New Zealand albino rabbits were used in this study. Three corneal models were tested: corneal incision, corneal epithelium scraping, and corneal suture.

In vivo confocal microscopy and ex vivo flow cytometry: new tools for assessing ocular inflammation applied to rabbit lipopolysaccharide-induced conjunctivitis.

Purpose: Lipopolysaccharide (LPS) may act as a key stimulatory agent in ocular surface diseases (OSDs) through TNF-alpha release. We used in vivo confocal microscopy (CM) and ex vivo flow cytometry, two new tools for assessing ocular inflammation induced by LPS.

Methods: We investigated a model of acute inflammation in rabbits by subconjunctival injection of LPS and developed new evaluation techniques for animal models: CM, to observe inflammatory infiltrates, and conjunctival impression cytology (IC) specimens processed with in vitro CM and flow cytometry for assessing TNF-alpha and TNF receptor-1 (TNFR-1) expression.

Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study.

Purpose: The aim of this study was to compare, in vivo on a rat model, two different preservatives- benzalkonium chloride (BAC) and polyquaternium-1 (PQ-1)-using new experimental approaches.

Methods: Thirty (30) eyes of 15 male Lewis rats were used in this study. Rats were randomly divided into five groups instilled twice a day for 11 days with eye drops containing different concentrations of preservatives, 0.

Comparative study of topical anti-allergic eye drops on human conjunctiva-derived cells: responses to histamine and IFN gamma and toxicological profiles.

Background: The purpose of the study was to compare toxic effects and responses to histamine and IFN gamma associated with the use of some widely used anti-allergic eye drops commercially available today.

Methods: For dynamic studies, the Wong-Kilbourne cell line was stimulated for 24 h with histamine or IFN gamma in the presence or absence of anti-allergic eye drops. Supernatants of histamine-stimulated cells were evaluated for the production of IL-6 and IL-8 by ELISA, while the expression of ICAM-1 was evaluated by flow cytometry on IFN gamma-stimulated cells.

In vitro comparison of cytoprotective and antioxidative effects of latanoprost, travoprost, and bimatoprost on conjunctiva-derived epithelial cells.

Purpose: In a previous study, it was demonstrated that in vitro in a human conjunctiva-derived cell line, latanoprost in its commercial presentation appeared to be less toxic than the benzalkonium chloride (BAC) it contains as a preservative. Through a microplate cytometry technique, the investigation was furthered by study of whether the three commercially available antiglaucoma prostaglandin analogs could protect the same cell line in vitro against BAC toxicity and whether an antioxidative mechanism could be involved in such prostaglandin effects.

Methods: Human conjunctiva-derived epithelial cells from the Chang cell line were exposed to three prostaglandins in their commercial presentation (latanoprost, travoprost, and bimatoprost) and to three concentrations of BAC (0.

In vitro study of inflammatory potential and toxicity profile of latanoprost, travoprost, and bimatoprost in conjunctiva-derived epithelial cells.

Purpose: Conjunctiva-derived epithelial cells were used to investigate, in vitro, the expression of various inflammation-associated markers known to be overexpressed in patients with glaucoma after contact with the three major commercially available eye drops containing prostaglandin analogues. The impact on cellular viability and apoptosis in the same cell line was evaluated, to address the possible proinflammatory and/or toxic origin of the most frequent clinical impairments induced by prostanoids (i.e.