Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics

Publisher: Society for Ocular Pharmacology and Therapeutics, Mary Ann Liebert

Description

  • Impact factor
    1.46
  • 5-year impact
    0.00
  • Cited half-life
    6.90
  • Immediacy index
    0.24
  • Eigenfactor
    0.00
  • Article influence
    0.35
  • Other titles
    Journal of ocular pharmacology and therapeutics (Online), Journal of ocular pharmacology and therapeutics
  • ISSN
    1557-7732
  • OCLC
    47295624
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Mary Ann Liebert

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's final version or publisher's version/PDF
    • Publisher's version/PDF may be used
    • On own website, institution's intranet, or institutional repository
    • Authors may deposit in funding agency designated repository after 12 months
    • Set statement to accompany deposit (see policy)
    • Publisher copyright and source must be acknowledged
    • NIH authors will have their final paper, (post peer review, copy-editing and proof-reading) deposited in PubMed Central on their behalf
  • Classification
    ​ blue

Publications in this journal

  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To evaluate the effects of benzalkonium chloride (BAK) on the blood-aqueous (BAB) and blood-retinal barriers (BRB) of pseudophakic eyes. Methods: Prospective, randomized, investigator-masked, comparative study. Patients were randomly assigned to preservative-free artificial tears or BAK-preserved artificial tears. One drop of artificial tears was instilled 4 times a day in the study eye, starting the day after randomization for 30 days. Anterior chamber flare was assessed by a laser flare meter (LFM) and macular thickness measurements were obtained with optical coherence tomography, before, 15, and 30 days after randomization. Results: A total of 44 healthy eyes of 44 pseudophakic volunteers were recruited. There were no significant differences regarding demographics (age, gender, and race distributions) and clinical characteristics (eye, mean intraocular pressure, and mean best-corrected visual acuity) between the 2 groups (P>0.05). No significant differences in baseline mean LFM values were observed (P=0.262). However, we detected a statistically significant increase in mean LFM measurements in the BAK-preserved group (11.4±5.1 ph/ms) (P=0.017) after 15 days. After 30 days, the BAK-preserved group maintained significantly higher flare values (11.9±5.9 ph/ms) compared with baseline (P=0.043). On the other hand, the preservative-free group showed mean flare values of 8.4±2.5 ph/ms, not significantly different from those obtained at baseline (P=1.00). We observed no statistically significant change in macular thickness measurements at days 15 and 30 in either group (P>0.05). Cystoid macular edema was not detected in this series. Conclusions: Our results suggest that a short-term exposure to BAK can cause disruption of the BAB, without altering the BRB in pseudophakic eyes.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: Retinal ischemic diseases primarily lead to damage of the inner retinal neurons. Electrophysiological studies also suggest impairment of the inner retinal neurons. Our recent studies with acute ocular hypertensive rats confirmed damage predominantly in the inner retinal layer along with the ganglion cell layer, changes that are ameliorated by the calpain inhibitor SNJ-1945. However, we do not know which specific neuronal cells in the inner retinal layer are damaged by calpains. Thus, the purpose of the present study was to identify specific calpain-damaged neuronal cells in the inner retina from acute ocular hypertensive rats. Methods: Intraocular pressure was elevated to 110 mm Hg for 40 min. One hour after ocular hypertension (OH), SNJ-1945 was administrated as a single oral dose of 50 mg/kg. Retinal function was assessed by scotopic electroretinography (ERG). Histological degeneration was evaluated by hematoxylin and eosin, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL), and immunostaining in thin sections and flat mounts of the retina. Calpain activation was determined by proteolysis of the calpain substrate α-spectrin. Results: OH caused calpain activation, increased TUNEL-positive staining, decreased thickness of the inner nuclear layer (INL), and decreased amplitudes of the ERG a- and b-waves and oscillatory potentials (OPs). SNJ-1945 significantly inhibited calpain activation and the decrease in ERG values. Interestingly, the changes in the b-wave and OPs amplitudes were significantly correlated to changes in the thickness of the INL. In the inner retinal layer, the numbers of rod bipolar, cone-ON bipolar, and amacrine cells were decreased after OH. SNJ-1945 suppressed the loss of cone-ON bipolar and amacrine cells, but did not inhibit the loss of rod bipolar cells. We also observed increased glial fibrillary acid protein-positive staining in the Müller cells after OH and the treatment with SNJ-1945. Conclusions: Calpains may contribute to ischemic retinal dysfunction by causing the loss of cone-ON bipolar and amacrine cells and causing the activation of Müller cells. Calpain inhibitor SNJ-1945 may be a candidate compound for treatment of retinal ischemic disease.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: The purpose of this study was to distinguish differences in gene expression between cells cultured from the juxtacanalicular trabecular meshwork (JCTM) and those from Schlemm's canal (SC), to gain clues to differences between those cell types, and to add to our baseline knowledge of gene expression differences in these cell types for later comparison between cells from nonprimary open-angle glaucoma (POAG) and POAG outflow tissues. Methods: A set of JCTM and SC cells was cultured from each of 2 donor eyes by an explant method, grown to passage 3, and frozen in liquid nitrogen. The cells were thawed, total RNA was extracted, and the probes made from total RNAs were hybridized to MICROMAX human cDNA microarray slides in 2 separate trials. Differentially expressed genes were analyzed using PubMed, Prosite, and IPA software, and the expression of several of the genes including intercellular adhesion molecule-1 (ICAM-1), tenascin, and β-spectrin was assessed by immunofluorescence. Results: Schlemm's canal cells differentially expressed ICAM-1, spectrin, complement, fibulin-1, and several genes consistent with an endothelial origin in both arrays, while the JCTM cells more often overexpressed genes consistent with contractile, matrix function, and neural character. At the same time, many genes highly expressed in the first array were not highly overexpressed in the second. One highly overexpressed gene in the JCTM in both arrays, that for heparan sulfate 3-O-sulfotransferase-1 precursor, is thought to be somewhat unique, and could affect the glycosaminoglycan functionality in the extracellular matrix (ECM). Conclusions: We found generally good agreement between the 2 array trials, but some contradictions as well. Many of the genes overexpressed in each cell type had been described in earlier work, but several were new. Tables of genes, grouped by cellular function, and the complete datasets are provided for the development of new hypotheses.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: This study evaluated the safety and efficacy of half-dose verteporfin combined with half-fluence photodynamic therapy (half-half photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Methods: This was a retrospective case series. Fourteen eyes with chronic CSC receiving half-half PDT were included in group 1. Another 28 eyes receiving half-dose verteporfin combined with standard fluence PDT were included in group 2 as a control group. Main outcome measures were the success rates, major complications, best-corrected visual acuity (BCVA), and central subfield foveal thickness (CFT) on optical coherence tomography (OCT) at 6 months in both groups. Success of treatment was defined as complete resolution of subretinal fluid on OCT after treatment without recurrence. Results: There was no significant difference between groups in their age, gender, duration of symptoms, baseline BCVA, baseline CFT, PDT spot size, and follow-up duration. The success rate was 64% (9/14 eyes) in group 1 and 93% (26/28 eyes) in group 2 at 6 months (P=0.031). No major complications were found in either group. Mean CFT showed significant reduction at 6 months in both groups (-115 μm and P<0.001 in group 1; -150 μm and P<0.001 in group 2). The mean BCVA in group 2 improved significantly (P<0.001) at 6 months. The mean BCVA in group 1 showed a trend of improvement but was not statistically significant (P=0.25) at 6 months. Conclusions: Half-half PDT is a feasible treatment for chronic CSC. However, there was a lower success rate at 6 months compared with the control group.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: This study evaluated the vitreous pharmacokinetics and vitreous bioavailability of memantine following posterior-subtenon administration (PST) compared to intravitreal (INT) and intravenous routes (INV) in rabbits. Methods: Vitreous pharmacokinetic analysis was performed on female New Zealand (NZ) albino rabbits after PST, INT, and INV administration and calculating the pharmacokinetic parameters that describe memantine vitreous distribution. The vitreous bioavailability (F) and the relative vitreous bioavailability of memantine was estimated after posterior-subtenon administration (Frel (pst/int)) and after intravenous route (Frel (inv/int)) compared with intravitreal administration. Relative vitreous bioavailability of memantine was also estimated following PST administration compared with vitreous concentrations after intravenous administration (Frel (pst/inv)). Results: Memantine kinetics in the vitreous of NZ albino rabbits after PST administration can be explained by a one-compartment model, which was characterized by a fast absorption process, and a short terminal half-life. Vitreous pharmacokinetics following INV administration was also characterized by a fast absorption process, a terminal half-life significantly longer than the subtenon route, and low area under the curve values. High vitreous bioavailability after PST was observed, and the relative vitreous bioavailability of memantine following PST administration (0.53%) was greater than for intravenous administration (0.02%). Conclusions: Our results suggest that memantine reaches the vitreous after PST administration by local diffusion. These data also show that local diffusion of the drug is responsible for greater vitreous availability of memantine following PST administration compared with INV administration.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: The trabecular meshwork (TM) outflow pathways of the aqueous humor show an increase in extracellular matrix in patients with primary open-angle glaucoma (POAG). The increase in TM extracellular matrix appears to be caused by transforming growth factor-β signaling and its downstream mediator connective-tissue growth factor (CTGF). Here we studied whether treatment with the prostaglandin F2α analog fluprostenol modulates the CTGF-mediated increase of the TM extracellular matrix. Methods: Human TM cells from 3 different donors were treated with CTGF (50 ng/mL) and/or fluprostenol (10(-6) M and 10(-7) M) and were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting. Cell supernatants of the treated cells were analyzed by zymography. Results: Treatment with CTGF induced the expression and synthesis of CTGF, fibronectin, collagen type IV and VI, while treatment with fluprostenol alone had no effects. The effects of CTGF were blocked by 1-h pretreatment with fluprostenol in a dose-dependent manner. Treatment with fluprostenol or combined fluprostenol/CTGF induced the activity of matrix metalloproteinase 2 (MMP2) in TM cells, whereas treatment with CTGF alone had no effects on MMP2 activity. Conclusions: Fluprostenol blocks the fibrotic effects of CTGF on human TM cells and increases the activity of MMP2. Both effects have the distinct potential to attenuate a CTGF-mediated increase in TM extracellular matrix in patients with POAG and any effects on TM outflow resistance that may result from that.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: The benzalkonium chloride (BAK) content of tafluprost ophthalmic solution (Tapros(®): tafluprost) has been reduced to balance corneal safety and preservative effectiveness (old formulation: 0.01%; new formulation: 0.001%). However, no reports have been published on its clinical effect. Therefore, we conducted a clinical research study to compare the safety of BAK-reduced tafluprost on the ocular surface with other prostaglandin ophthalmic solutions. Methods: This clinical study included 28 glaucoma patients (28 eyes) with a treatment history of latanoprost ophthalmic solution (Xalatan(®)) or travoprost ophthalmic solution (Travatan Z(®)), who presented with corneal epithelial disorders. The subjects were switched to BAK-reduced tafluprost, and its effect on the ocular surface was examined after 1 and 2 months of treatment [using fluorescein staining score, hyperemia, tear film breakup time, and intraocular pressure (IOP) lowering]. Results: In all analyzed subjects (N=27), the fluorescein staining score was significantly improved after switching to BAK-reduced tafluprost (P<0.0001). Conversely, the IOP-lowering effect was not notably changed. The subjects switched from latanoprost (n=10) showed significant improvement in fluorescein staining score (P<0.05) as well as in IOP lowering (P<0.01). The subjects switched from travoprost (n=17) also showed significant improvement in fluorescein staining score (P<0.001), but without a significant change in IOP lowering. Conclusions: Tafluprost with reduced BAK has potential as a superior antiglaucoma drug, not only for its IOP-lowering effect, but also for its good corneal safety profile.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Myocilin is a secreted glaucoma-associated protein, specifically induced by dexamethasone in human trabecular meshwork cells, where it was discovered. Myocilin is expressed in several tissues of the body, but it causes disease only in the eye. The protein contains two domains: an N-terminal region with significant homologies to nonmuscle myosin, and a C-terminal region, which is similar to the olfactomedin proteins. Forty percent of myocilin undergoes an intracellular endoproteolytic cleavage by calpain II, a calcium-dependent cysteine protease, which releases the 2 domains. The protein is known to interact with intracellular and extracellular matrix proteins, and some is released into the extracellular space associated with exosomes. Myocilin mutations are linked to glaucoma and induce elevated intraocular pressure. Most of the glaucoma-causative mutations map to the olfactomedin domain, which appears to be a critical domain for the function of the protein. Myocilin mutants are misfolded, aggregate in the endoplasmic reticulum, and are not secreted. Overexpression of myocilin and of its mutants in primary human trabecular meshwork cells triggers changes in the expression of numerous genes, many of which have been known to be involved in mechanisms important for the physiology and pathology of the tissue. Here we review recent studies from our laboratory and those of others that deal with trabecular meshwork genes, which are altered by the overexpression of wild-type and glaucoma-causative mutant myocilin genes.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the antioxidant properties and biological functions of ascorbic acid (AA) on trabecular meshwork (TM) cells. Methods: Primary cultures of porcine TM cells were supplemented for 10 days with increasing concentrations of AA. Antioxidant properties against cytotoxic effect of H2O2 were evaluated by monitoring cell viability. Redox-active iron was quantified using calcein-AM. Intracellular reactive oxygen species (iROS) production was quantified using H2DCFDA. Ferritin and cathepsin protein levels were analyzed by Western blot. Autophagy was evaluated by monitoring lipidation of LC3-I to LC3-II. Lysosomal proteolysis and cathepsins activities were quantified using specific fluorogenic substrates. Results: AA exerts a dual effect against oxidative stress in TM cells, acting as an anti-oxidant or a pro-oxidant, depending on the concentration used. The pro-oxidant effect of AA was mediated by free intracellular iron and correlated with increased protein levels of ferritin and elevated iROS. In contrast, antioxidant properties correlated with lower ferritin and basal iROS content. Ascorbic acid supplementation also caused induction of autophagy, as well as increased lysosomal proteolysis, with the latter resulting from higher proteolytic activation of lysosomal cathepsins in treated cultures. Conclusions: Our results suggest that the reported decrease of AA levels in plasma and aqueous humor can compromise lysosomal degradation in the outflow pathway cells with aging and contribute to the pathogenesis of glaucoma. Restoration of physiological levels of vitamin C inside the cells might improve their ability to degrade proteins within the lysosomal compartment and recover tissue function.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To study the visual outcomes and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with ranibizumab (Lucentis) and/or bevacizumab (Avastin) and were subsequently switched to aflibercept (VEGF Trap-Eye; Eylea). Methods: Retrospective study of patients who received intravitreal aflibercept from December 2011 to December 2012 and had previous anti-vascular endothelial growth factor treatment for AMD. The main outcome measures were best-corrected visual acuity (BCVA) and CMT as measured by optical coherence tomography. Results: The study population included 30 patients aged 80.4±1.45 (mean±SEM) who received 6.27±0.37 (range 4-11) aflibercept injections. Eighteen patients had previously received only bevacizumab (12.4±2.18 injections), 2 had received only ranibizumab (19±6 injections), and 10 had received both ranibizumab and bevacizumab (mean 19.3 injections). BCVA logMAR at the initial visit (aflibercept initiation) was 0.506±0.054 (mean VA 20/64), and then, follow ups at 1-month 0.504±0.055 (20/64) P=0.903, 3-months 0.458±0.061 (20/57) P=0.112, 6-months 0.413±0.071 (20/52) P=0.036, and 12-months 0.521±0.076 (20/66) P=0.836. CMT at the initial visit was 261±10.9, and then, at 1-month 238±12.4 P=0.021, 3-months 245±10.6 P=0.102, 6-months 245±10.4 P=0.099, and 12-months 237±10.2 P=0.012. Results were similar in a subset of patients (n=15) with central macular edema or submacular fluid at aflibercept initiation. While on aflibercept, 2 patients developed intraocular pressure increases that required treatment. Conclusions: These findings demonstrate a significant decrease in CMT but no statistically significant improvement in BCVA through the 12-month follow up in patients previously treated who were switched to aflibercept for AMD. Patients may develop ocular hypertension after multiple aflibercept injections.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Microfibrils are macromolecular aggregates located in the extracellular matrix of both elastic and nonelastic tissues that have essential functions in formation of elastic fibers and control of signaling through the transforming growth factor beta (TGFβ) family of cytokines. Elevation of systemic TGFβ and chronic activation of TGFβ signal transduction are associated with diseases caused by mutations in microfibril-associated genes, including FBN1. A role for microfibrils in glaucoma is suggested by identification of risk alleles in LOXL1 for exfoliation glaucoma and mutations in LTBP2 for primary congenital glaucoma, both of which are microfibril-associated genes. Recent identification of a mutation in another microfibril-associated gene, ADAMTS10, in a dog model of primary open-angle glaucoma led us to form the microfibril hypothesis of glaucoma, which in general states that defective microfibrils may be an underlying cause of glaucoma. Microfibril defects could contribute to glaucoma through alterations in biomechanical properties of tissue and/or through effects on signaling through TGFβ, which is well established to be elevated in the aqueous humor of glaucoma patients. Recent work has shown that diseases caused by microfibril defects are associated with increased concentrations of TGFβ protein and chronic activation of TGFβ-mediated signal transduction. In analogy with other microfibril-related diseases, defective microfibrils could provide a mechanism for the elevation of TGFβ2 in glaucomatous aqueous humor. If glaucoma shares mechanisms with other diseases caused by defective microfibrils, such as Marfan syndrome, therapeutic interventions to inhibit chronic activation of TGFβ signaling used in those diseases may be applied to glaucoma.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is a primary risk factor associated with POAG. Increased aqueous humor (AH) outflow resistance through the trabecular meshwork (TM) results in elevated IOP in POAG patients. Resistance to AH outflow is associated with increased accumulation of extracellular matrix (ECM) proteins in the TM. In addition, levels of transforming growth factor-beta2 (TGF-β2) are elevated in the AH and TM tissue of POAG patients. Elevated levels of TGF-β2 in other tissues have been associated with fibrosis and increased tissue stiffness. However, locally produced effectors that maintain homeostatic relationships must also be present. Bone morphogenetic proteins (BMPs) serve this purpose in the TM as they inhibit TGF-β2-induced ECM changes in TM cells. This review article first describes the TGF-β superfamily of growth factors including BMPs and their canonical and noncanonical signaling pathways. The article then addresses the role of TGF-β2 in the pathophysiology of POAG as related to the ECM and ECM crosslinking enzymes. This is followed by a discussion of potential homeostatic control mechanisms of TGF-β2 signaling in the TM including the inhibitory role of BMP-4 and BMP-7. We then describe the relationship of TGF-β2 and BMPs in TM fibrosis including the role of antagonists. Lastly, in future directions, we identify potential future studies that explore new and unique cellular interactions within the TM for potential therapeutic interventions.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: Schlemm's canal (SC) inner wall is adjacent to the juxtacanalicular trabecular meshwork (TM) over their entire circumference. We seek to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys. Methods: A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-μm outer diameter and an LED-lighted tip. A 6-0 prolene suture was used for the exact localization of SC. Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC. Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned noncontact endoscopic imaging system and 50 mHz ultrasound biomicroscopy (UBM). Results: A 360° catheterization and injection of dye into SC was achieved. Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM. Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter. Conclusions: A modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization. Further studies comparing different delivery methods of the vector/transgene into the SC using canaloplasty are needed.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the safety of trypan blue, brilliant blue G (BBG), Evans blue (EB), patent blue, Chicago blue (CB), and bromophenol blue (BB), with and without halogen and xenon light exposure. Methods: All dyes were diluted in a balanced saline solution at a concentration of 0.5%. Cells of the human RPE line ARPE-19 and rat RGC5 were exposed to vital dyes for 5 min. Experiments with and without xenon or halogen illumination were performed. The viability of ARPE-19 and RGC5 cells was determined at 12, 24, or 120 h by a cell proliferation assay using WST-1 reagent. The apoptotic events as well as cell numbers were registered for 72 h and counted by time-lapse videomicroscopy. Results: There was no evidence of ARPE-19 or RGC5 toxicity, immediate (0 and 24 h) or delayed (120 h), following exclusive exposure to each single dye. After halogen light exposure, ARPE-19 cell lines did not show any significant toxicity, except for when they were exposed to EB. After xenon illumination, ARPE-19 cells showed a marked decrease in cell viability when exposed to EB or CB and a moderate decrease when exposed to BBG and BB. After xenon illumination, RGC5 cells showed the highest decrease in cell viability when exposed to EB and CB; BB caused the same decrease in cell viability as in ARPE-19 cells. Conclusion: Interaction of light from endo-illumination source and blue vital dyes may increase the risk of retinal toxicity.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the short-term adverse effects of using rebamipide for the treatment of dry eye by assessing visual function and optical quality. Methods: This interventional noncomparative study included 14 right eyes of 14 healthy volunteers. Serial measurements of visual acuity (VA) and higher-order aberrations were obtained prior to instillation of the rebamipide suspension (baseline) and immediately after and at 5, 10, 20, and 30 min after instillation. Functional VA measurement was performed over a 60-s period with the subject blinking naturally. Ocular aberrations were measured for 10 s while the subject was told not to blink, but no topical anesthesia was applied. Each patient also filled out a questionnaire exploring the rebamipide-associated adverse effects. Results: There was no significant difference between functional VA measured at baseline and at each time point after the instillation of rebamipide. In contrast, the root mean square of third-order and total higher-order aberrations increased significantly immediately after drug instillation (P<0.05). The severity of higher-order aberrations at baseline was similar to that observed at 5, 10, 20, and 30 min after instillation (P>0.05). Conclusions: The transient reduction in optical quality immediately after administration of rebamipide is corrected by the patient's natural blink reflex. The adverse effects observed in this study do not outweigh the benefits of rebamipide treatment.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: The aim of the current study is to compare the effects of two corticosteroids, prednisolone acetate 1% (PA) and loteprednol etabonate 0.5% (LE), for the treatment of benzalkonium chloride (BAC)-induced dry eye syndrome (DES) in rats. Methods: DES was established by topical administration of 0.2% BAC, a commonly used preservative in ophthalmic drugs, for 1 week. Rats were divided into 3 groups just after establishment of DES: PA-treated (Group 1, n=10), LE-treated (Group 2, n=10), and vehicle-treated (Group 3, n=10). Rats were treated by topical administration of PA, LE, or vehicle twice daily for 1 week. The Schirmer test, break-up time score, Fluorescein staining, Rose Bengal staining, and inflammatory index scoring (IIS) tests were performed at all weeks. After the end of the study, eyes of the rats were enucleated and analyzed using light microscopy. Results: The mean aqueous tear volume was significantly increased in both PA- and LE-treated rats (P<0.05), although decreased in vehicle-treated rats (P>0.05). Histologically, diffuse inflammatory cell infiltration was observed in vehicle-treated rats, while inflammation induced by BAC was almost completely resolved in both PA- and LE-treated groups. Conclusions: In the current study, we showed that both PA and LE are effective treatments in a rat model of BAC-induced DES, which is commonly observed in clinics. No significant differences were observed between the 2 corticosteroids in the efficacy of BAC-induced type of DES treatment.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014;
  • Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014; 30(1):1.
  • [show abstract] [hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the effect of 2 commonly used mydriatics on choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: In this prospective study, 90 healthy subjects were enrolled. The participants were randomly divided into 3 groups based on the application of drops. One eye of each subject received a drop of tropicamide 1% in the tropicamide group (n=30), a drop of phenylephrine 2.5% in the phenylephrine group (n=30), and a drop of artificial tear in the control group (n=30). Drops were given thrice at 5 min intervals. Subfoveal choroidal thickness (SFCT) was measured using EDI-OCT before and at 45 min after drop application in both the dilated eye and nondilated contralateral eye. Results: The SFCT was significantly decreased after drop instillation in both the dilated eye and contralateral eye in the tropicamide group (P<0.001 and P=0.001, respectively) and in the phenylephrine group (P<0.001 and P=0.001, respectively). However, the SFCT did not significantly differ after drop instillation in either the dropped eye or contralateral eye in the control group (P=0.108 and P=0.695, respectively). Conclusion: The findings of the present study revealed that tropicamide and phenylephrine cause a decrease in choroidal thickness.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 01/2014;

Related Journals