The DNA topoisomerase II inhibitor amsacrine as a novel candidate adjuvant in a model of glaucoma filtration surgery.

Treatments for refractory glaucoma include trabeculectomy, in which a filtering bleb is created to reduce aqueous pressure. Mitomycin C (MMC) is often used as an adjuvant to reduce post-trabeculectomy bleb scarring and consequent failure. However, scarring sometimes still occurs.

Systemic expression of Alu RNA in patients with geographic atrophy secondary to age-related macular degeneration.

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is characterized by irreversible loss of macular retinal tissue and retinal pigment epithelium (RPE) cells. Several studies have revealed that accumulation of Alu RNA in RPE cell causes RPE cell degeneration in AMD. In the present study, systemic Alu RNA expression levels were determined in 33 subjects with GA and 40 control subjects using a proprietary Alu RNA quantification method.

The effectiveness of colchicine combined with mitomycin C to prolong bleb function in trabeculectomy in rabbits.

Purpose: To investigate the potential of colchicine to improve bleb function after trabeculectomy.

Methods: To find the maximum usable colchicine concentration, an ocular irritation study was performed with the Draize test at concentrations of 0.001%, 0.

Development of a highly sensitive and reliable enzyme-linked immunosorbent assay for MUC5AC in human tears extracted from Schirmer strips.

Purpose: Reliable measurement of MUC5AC in human tears is essential for elucidation of the pathophysiological role of MUC5AC in dry eye disease. The purpose of this study was to develop a sensitive and reliable method for measurement of MUC5AC in human tear samples extracted from Schirmer strips by modifying a commercially available ELISA.

Methods: MUC5AC was extracted from Schirmer strips containing human tears by PBS with various concentrations of polysorbate 20.

Spermidine Oxidation-Mediated Degeneration of Retinal Pigment Epithelium in Rats.

Retinal pigment epithelium (RPE) degeneration is a crucial event in dry age-related macular degeneration and gyrate atrophy. The polyamine spermidine has been shown to induce RPE cell death in vitro. The present study aimed to establish a novel in vivo model of spermidine-induced RPE degeneration and to determine whether spermidine-induced RPE cell death involves oxidative mechanisms.

Comparison of Short-Term Effects of Diquafosol and Rebamipide on Mucin 5AC Level on the Rabbit Ocular Surface.

Purpose: To investigate the short-term effects of 2 new secretagogue eye drops for dry eye, 3% diquafosol tetrasodium ophthalmic solution (diquafosol) and 2% rebamipide ophthalmic suspension (rebamipide), on the concentration of mucin 5AC (MUC5AC) in rabbit tear fluid and conjunctival goblet cells.

Methods: One dose of artificial tears, diquafosol or rebamipide, was instilled into 8 eyes of Japanese white rabbits. MUC5AC concentration in the tear fluid was examined using the enzyme-linked immunosorbent assay 15 min after instillation and compared with 8 untreated controls.

A Novel Model of Meibomian Gland Dysfunction Induced with Complete Freund's Adjuvant in Rabbits.

A novel meibomian gland dysfunction (MGD) model induced by the injection of complete Freund's adjuvant (CFA) in rabbits was developed to facilitate the understanding of the pathophysiology of MGD with meibomitis. In addition, we sought to evaluate treatment with steroid eye drops in this model. Male Japanese white rabbits were subcutaneously injected with CFA into the upper eyelid margin.

The effects of oral and topical corticosteroid in rabbit corneas.

Background: To determine the most effective route of administration of corticosteroids in the treatment of ocular surface disease, by characterizing the difference between oral prednisolone and topical dexamethasone administration using an animal model.

Methods: Pharmacokinetic analyses determined the corticosteroid concentrations in the normal ocular tissues of rabbits after oral or topical administration of corticosteroids using LC-MS/MS. In wound healing analyses, the area of the epithelial defect created by keratectomy using a 6-mm trephine was calculated with an image analyzer using an orally or topically steroid-administrated animal model.

Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.

Purpose: A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD).

Methods: Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks.

Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients.

Purpose: We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients.

Patients And Methods: A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye.

Linoleic acid content of human meibum is associated with telangiectasia and plugging of gland orifices in meibomian gland dysfunction.

To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.

Beneficial protective effect of pramipexole on light-induced retinal damage in mice.

We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h).

Meibum Color and Free Fatty Acid Composition in Patients With Meibomian Gland Dysfunction.

Purpose: We measured the components of meibum in patients with meibomian gland dysfunction (MGD) and control subjects and then examined the relation between meibum composition and clinical parameters.

Methods: Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.

Expression of the P2Y₂ receptor on the rat ocular surface during a 1-year rearing period.

Purpose: P2Y2 receptors are expressed on ocular surface tissues. Diquafosol ophthalmic solution (DIQUAS(®) ophthalmic solution 3 %; Santen Pharmaceutical Co., Ltd.

Rapid identification of fatty acids and (O-acyl)-ω-hydroxy fatty acids in human meibum by liquid chromatography/high-resolution mass spectrometry.

We report a rapid liquid chromatography/quadrupole Orbitrap Fourier transform mass spectrometry (LC-FTMS) method for identifying free fatty acids (FAs) and (O-acyl)-ω-hydroxyFAs (OAHFAs) in human meibum without derivatization. Meibum is a lipid-rich secretion and an important component of the tear film lipid layer. FAs are commonly detected by gas chromatography (GC) or GC/MS after methyl ester derivatization.

OCT evaluation of neuroprotective effects of tafluprost on retinal injury after intravitreal injection of endothelin-1 in the rat eye.

Purpose: To determine whether optical coherence tomography (OCT) is a useful technique to monitor retinal damage and to evaluate the neuroprotective effect of topical tafluprost in a rat model of intravitreal endothelin-1 (ET-1) injection.

Methods: A single intravitreal injection of ET-1 (0.2-200 pmol/eye) was performed in one eye.

Ocular hypotensive efficacy of Src-family tyrosine kinase inhibitors via different cellular actions from Rock inhibitors.

We investigated the effects of Src-family tyrosine kinase (SFK) inhibitors on intraocular pressure (IOP) and trabecular meshwork (TM) cells. The SFK inhibitors, PP2, PP1, and damnacanthal, significantly lowered IOP from baseline following intracameral injection in ocular normotensive rabbits, and PP2 decreased trans-epithelial electrical resistance (TEER) of TM cell layers in a dose-dependent manner ranging from 0.1 μM to 100 μM.

Changing trends in the treatment of dry-eye disease.

Introduction: Dry eye is a visually disabling disease encountered in many countries with a wide variation of treatment practices all over the world. On that front, the 2007 Report of the International Dry Eye WorkShop (DEWS) reviewed the current knowledge on all aspects of dry-eye disease (DED), in an evidence-based manner, and outlined the trends and recommendations in the treatment of DED on the basis of disease severity.

Areas Covered: This review mainly focuses on treatments for DED based on severity as recommended in the DEWS report, particularly artificial eye drops, hyaluronate sodium eye drops, autologous serum, anti-inflammatory eye drops including cyclosporine and steroids, and mucin secretagogues.

[Effect of flavin adenine dinucleotide on ultraviolet B induced damage in cultured human corneal epithelial cells].

This study evaluated the effects of flavin adenine dinucleotide (FAD) on ultraviolet B (UV-B)-induced damage in cultured human corneal epithelial (HCE-T) cells. The cultured HCE-T cells were treated with 0.003125-0.

Diquafosol ophthalmic solution for dry eye treatment.

Introduction: There has been rapid progress in our understanding of dry eye pathogenesis, as well as the development of improved diagnostic clinical tests. Various types of dry eye treatment drugs have been developed. This review summarizes the basic and clinical research carried out in the development of diquafosol for ophthalmic use.

Report of the TFOS/ARVO Symposium on global treatments for dry eye disease: an unmet need.

In September 2010, a Symposium in Florence, Italy, was held to address the unmet need for global treatments for dry eye disease (DED). It was sponsored by The Tear Film & Ocular Surface Society (TFOS; www.TearFilm.

Flt1 and Flk1 mediate regulation of intraocular pressure and their double heterozygosity causes the buphthalmia in mice.

Flt1 and Flk1 are receptor tyrosine kinases for vascular endothelial growth factor-A which play a crucial role in physiological and pathological angiogenesis. To study genetic interaction between the Flt1 and Flk1 genes, we crossed between Flt1 and Flk1 heterozygous (Flt1(+/-) and Flk1(+/-)) mice. We found that Flt1; Flk1 double heterozygous (Flt1(+/-); Flk1(+/-)) mice showed enlarged eyes similar to the buphthalmia detected in human congenital glaucoma with elevation of intraocular pressure (IOP).

Beneficial pharmacological effects of selective glucocorticoid receptor agonist in external eye diseases.

Purpose: Glucocorticoids exert their actions via the glucocorticoid receptor through at least 2 intracellular mechanisms, known as transrepression and transactivation. It has been hypothesized that transrepression is the basis of their anti-inflammatory effects, whereas transactivation has been assumed to cause their side effects. ZK209614, a recently identified, novel selective glucocorticoid receptor agonist, exerts strong transrepression and weak transactivation.