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

Current impact factor: 1.47

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 1.47
2013 Impact Factor 1.42
2012 Impact Factor 1.293
2011 Impact Factor 1.509
2010 Impact Factor 1.609
2009 Impact Factor 1.457
2008 Impact Factor 1.37
2007 Impact Factor 1.034
2006 Impact Factor 1.035
2005 Impact Factor 0.897
2004 Impact Factor 1.228
2003 Impact Factor 1.383
2002 Impact Factor 1.051
2001 Impact Factor 1.085
2000 Impact Factor 0.757
1999 Impact Factor 0.763
1998 Impact Factor 0.841
1997 Impact Factor 0.763
1996 Impact Factor 0.937
1995 Impact Factor 0.514

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.56
Cited half-life 5.80
Immediacy index 0.34
Eigenfactor 0.00
Article influence 0.43
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 can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • On author's personal website
    • On institutional repository, pre-print server or research network after 12 months embargo
    • Publisher's version/PDF cannot be used
    • 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
    • Must link to publisher version with DOI
  • Classification
    green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: A study was conducted to evaluate the inhibitory effects of vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, BC001, against laser-induced choroidal neovascularization (CNV). We induced the experimental CNV in rhesus monkey eyes using laser photocoagulation. Monkeys were randomly assigned to 4 groups that received a single intravitreal administration of BC001 at 0 (vehicle-treated group), 0.05, 0.2, and 0.5 mg/eye. Fundus fluorescein angiography, optical coherence tomography, and histological studies were used for evaluations. The ocular recovery was determined by comparing changes of fluorescein leaking area and thickness of disrupted retina around the laser burn spot before and after drug administration. Choroidal blood vessels were stained and quantified by lectin staining. Hematoxylin and eosin staining was performed to determine the general histological complications. An intravitreal injection of BC001 at 0.05, 0.2, and 0.5 mg per eye at 20 days after laser burn significantly reduced the CNV-induced fluorescein leakage, retina pathology, and aberrant choroidal vessel growth and did not change intraocular pressure or induce any immune response. BC001 confers significant inhibitory effects against laser-induced CNV in rhesus monkeys, thereby suggesting that prevention of VEGFR2 activation may be promising as an alternative therapeutic target for exudative age-related macular degeneration.
    No preview · Article · Sep 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To compare the efficacy of intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME) in vitrectomized eyes with DME without vitrectomy eyes. This retrospective comparative study evaluated the efficacy of IVTA treatment of DME in 26 consecutive eyes (23 patients). Changes in mean best-corrected visual acuity (VA) and mean central retinal thickness (CRT) were retrospectively evaluated before IVTA and during the 6-month period after IVTA. Subjects were divided into 2 groups: 13 consecutive eyes (11 patients) with proliferative diabetic retinopathy or DME that underwent vitrectomy (vitrectomized group), and 13 consecutive eyes (12 patients) with DME who received IVTA, but did not undergo vitrectomy (nonvitrectomized group). In the vitrectomized group, there was a significantly decreased CRT for up to 4 months as compared to the thicknesses before IVTA. In the nonvitrectomized group, there was a significantly decreased CRT for up to 5 months after IVTA. In both groups, there was significant improvement in the VA for up to 4 months after IVTA. IVTA may represent a valid treatment option for DME, even in vitrectomized eyes.
    No preview · Article · Sep 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To assess the usefulness of 0.0015% tafluprost and 0.5% timolol fixed-dose combination (TT-FDC) for glaucoma, the ocular hypotensive effect of TT-FDC and concentration of tafluprost and timolol in the aqueous humor were compared with those of the concomitant administration of 0.0015% tafluprost and 0.5% timolol with or without an appropriate administration interval. The ocular hypotensive effect was assessed by intraocular pressure (IOP) measurement in cynomolgus monkeys. Drug penetration into the aqueous humor was estimated by the concentrations of tafluprost acid (active metabolic form of tafluprost) and timolol, which were measured using liquid chromatography-tandem mass spectrometry after administration of tafluprost and timolol to Sprague Dawley rats. The ocular hypotensive effect of TT-FDC was equivalent to that of the concomitant administration of timolol and tafluprost at a more than 5-min interval in monkeys. However, the ocular hypotensive effect of the concomitant administration of timolol and tafluprost without an interval (-2.8 ± 0.2 mmHg at peak IOP reduction) was significantly weaker compared with TT-FDC (-4.3 ± 0.5 mmHg at peak IOP reduction, P = 0.008 vs. concomitant administration of timolol and tafluprost) in monkeys. The aqueous humor concentration of the second administered drug (tafluprost) was not affected by the dosing conditions, whereas the concentration of the first instilled drug (timolol) without the interval was lower than that with a 5-min interval (1,200 ng · h/mL vs. 1,890 ng · h/mL in AUC0-4) in rats. TT-FDC demonstrates a clear benefit by preventing efficacy loss without an appropriate interval in experimental animal models.
    Preview · Article · Sep 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To evaluate effects of a novel multi-ingredient artificial tear formulation containing carboxymethylcellulose (CMC) and hyaluronic acid (HA) in a murine dry eye model. Dry eye was induced in mice (C57BL/6) using an intelligently controlled environmental system (ICES). CMC+HA (Optive Fusion™), CMC-only (Refresh Tears(®)), and HA-only (Hycosan(®)) artificial tears and control phosphate-buffered saline (PBS) were administered 4 times daily and compared with no treatment (n = 64 eyes per group). During regimen 1 (prevention regimen), mice were administered artificial tears or PBS for 14 days (starting day 0) while they were exposed to ICES, and assessed on days 0 and 14. During regimen 2 (treatment regimen), mice exposed to ICES for 14 days with no intervention were administered artificial tears or PBS for 14 days (starting day 14) while continuing exposure to ICES, and assessed on days 0, 14, and 28. Corneal fluorescein staining and conjunctival goblet cell density were measured. Artificial tear-treated mice had significantly better outcomes than control groups on corneal staining and goblet cell density (P < 0.01). Mice administered CMC+HA also showed significantly lower corneal fluorescein staining and higher goblet cell density, compared with CMC (P < 0.01) and HA (P < 0.05) in both regimens 1 and 2. The artificial tear formulation containing CMC and HA was effective in preventing and treating environmentally induced dry eye. Improvements observed for corneal fluorescein staining and conjunctival goblet cell retention suggest that this combination may be a viable treatment option for dry eye disease.
    No preview · Article · Aug 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To investigate the efficacy of 2-phenyl-APB-144 (APB)-induced retinopathy in a rat model and its underlying mechanisms, with a particular focus on retinal pigment epithelium (RPE) degeneration. Electroretinograms (ERGs) were evaluated in APB-administered rats. In ARPE-19 cells, cathepsin, and autophagy marker LC3 were analyzed by western blotting or immunohistochemistry. Organelle pH alterations were detected by Acridine Orange Staining. Endoplasmic reticulum stress-dependent or -independent cell death signaling was analyzed by reporter gene assays of activating transcription factor 4 (ATF4), immunoglobulin heavy-chain binding protein (BiP), inositol-requiring enzyme 1α (IRE1α), quantitative reverse transcription-polymerase chain reaction of CHOP mRNA, and the effects of pharmacological eukaryotic initiation factor 2α (eIF2α) dephosphorylation inhibitor, Salubrinal. The pharmacological effects of Salubrinal were examined by fluorophotometry, electrophysiology, and histopathology. APB-induced ERG amplitude reduction and fluorescein permeability enhancement into the vitreous body of rats were determined. In ARPE-19 cells, APB-induced organelle pH alterations, imbalances of procathepsin and cathepsin expression, the time-dependent accumulation of LC3-II, and the translational activation of ATF4 were determined. Salubrinal protected against APB-induced cell death and inhibited ATF4 downstream factor CHOP mRNA induction. In APB-induced rat retinopathy, systemic Salubrinal alleviated the enhanced fluorescein permeability into the vitreous body from the RPE, the reductions in ERG amplitudes, and RPE degeneration. Organelle pH alterations and autophagy impairments are involved in APB-induced RPE cell death. Inhibition of eIF2α dephosphorylation protected the RPE in vivo and in vitro. These findings suggested that APB-induced retinopathy is a valuable animal model for exploring the mechanism of RPE-driven retinopathy.
    No preview · Article · Aug 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.
    No preview · Article · Aug 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: The purpose of this laboratory study was to assess the effect of povidone-iodine (PI) use topically on the conjunctiva in regard to needle bore contamination and to compare these results with our previous findings from an evaluation of bacterial contamination following gatifloxacin and moxifloxacin administration. We performed 100 conjunctival 27-gauge needle penetrations of both eyes of 13 fresh cadavers. Eyes were then soaked in 10% PI, after which conjunctiva was again penetrated 100 times. After conjunctival penetration, the needles were irrigated, and the irrigant was assessed for bacterial growth. Results were compared with previous work assessing fluoroquinolone effectiveness through the same model. We observed a 28% (P = 0.003) decrease in bacterial growth and 40% (P < 0.0001) decrease in colony counts after PI placement. Differences between the effect of PI versus moxifloxacin and gatifloxacin were not statistically significant. There is a greater decrease in bacterial load after treatment with PI for surface cultures than for cultures obtained through a needle bore passed through the conjunctiva. PI is a superior approach to topical antibiotics to decrease conjunctival bacterial load.
    No preview · Article · Aug 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: Caused by the parasite Toxoplasma gondii, ocular toxoplasmosis (OT) is the most common form of posterior infectious uveitis. Combined antiparasitic therapy is the standard treatment for OT, but several other schemes have been proposed. The purpose of the present study was to review the literature on the treatment of OT and provide ophthalmologists with up-to-date information to help reduce OT-related visual morbidity. In conclusion, no ideal treatment scheme was identified; currently prescribed therapeutic schemes yield statistically similar functional outcomes.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To evaluate the efficacy and safety of preservative-free triamcinolone acetonide (Triesence) for the treatment of macular edema. A retrospective study was conducted on patients who attended a tertiary retinal clinic from June 2009 to July 2012 with macular edema due to various causes. Patients who received at least 1 intravitreal Triesence injection and completed 6 months of follow-up were recruited. Data, including best-corrected Snellen visual acuity, central macular thickness (CMT), intraocular pressure (IOP), and adverse events (AEs), were collected at baseline, week 1, month 1, month 3, and month 6 after initiation of treatment. Snellen visual acuity was converted to visual acuity score (VAS) for statistical analysis using paired t-tests and linear regression. One hundred two eyes from 102 patients were included in the study. Mean VAS was significantly improved at all follow-up time points compared to baseline (P≤0.002), with highest mean gain at month 1 (6.1±8.9 letters). Mean CMT decreased significantly at all follow-up points compared to baseline (P≤0.0005), with the greatest reduction at week 1 (146.6±109.4 μm). A total of 22 AEs were observed, and IOP elevation was the most common AE related to Triesence treatment (17/22, 77.3%). No sterile or infectious endophthalmitis was observed. Intravitreal Triesence improves visual acuity and reduces macular thickness in eyes with macular edema from various causes. Treatment-associated IOP elevation was manageable with antiglaucoma medications. There were no serious vision-threatening complications associated with intravitreal Triesence therapy during the study period.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: Atropine 0.01% eyedrops have been shown to slow childhood myopic progression in primarily Asian populations. We studied its effects on an ethnically diverse population over a broad range of myopia. A retrospective case-control study was performed on 60 children (6-15 years) with initial myopic spherical equivalents from -0.25 to -8.00 diopters (D). The primary outcome was the rate of myopic progression per year. Secondary outcomes were the proportion of subjects with slow or rapid myopic progression, atropine-related side effects, and rates of myopic progression for subgroups with low, moderate, or higher initial myopia. The average initial age (10.2 years) and refraction (-2.0 D) were identical between groups. After 1.1±0.3 years follow-up, atropine subjects had significantly lower rates of myopic progression (-0.1±0.6 D/year) than controls (-0.6±0.4 D/year) (P=0.001), including 24 of 32 (75%) with slow progression ≤-0.25 D/year versus only 5 of 28 (18%) controls. Three atropine and 4 control subjects had rapid progression ≥-1.00 D/year. For subjects with low initial myopia (≤-1.00 D), 9 of 11 (82%) atropine subjects had plano or slightly hyperopic refractive changes after 1 year, while 8 of 8 (100%) controls were more myopic. Only 3 atropine subjects complained of intermittent blur or light sensitivity, not symptomatic enough to discontinue treatment. Atropine 0.01% significantly reduced the rate of myopic progression over 1 year with minimal side effects. It appears most effective in children with low initial myopia and may not control rapid myopic progression in some patients. Stronger concentrations of atropine may be required to slow rapid myopic progression.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To determine whether curcumin offers neuroprotection to minimize the apoptosis of neural cells in the retina of diabetic rats. Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal histology, apoptosis of neural cells in the retina, electroretinograms, and retinal glutamate content were evaluated after 12 weeks. Retinal levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), and cleaved caspase-3 were determined by Western blot analysis. The amplitudes a-wave, b-wave, and oscillatory potential were reduced by diabetes, but curcumin treatment suppressed this reduction of amplitudes. Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats, but was significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced in curcumin-treated rats. Curcumin attenuated diabetes-induced apoptosis in retinal neurons by reducing the glutamate level and downregulating CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of patients with diabetes mellitus.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics

  • No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To evaluate the effects of fluoroquinolone-based antibacterial ophthalmic solutions on cell proliferation in vitro and corneal wound healing in vivo. Staten's Serum institute rabbit corneal cells were exposed to phosphate-buffered saline, 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin, for 2 min, following which the cells were incubated without the drug. The cell viability was evaluated after 24 or 72 h of incubation. Rabbit corneal epithelial abrasion models created using n-heptanol were instilled with saline or fluoroquinolone-based solutions 7 times at 30-min intervals, following which corneal epithelial wound healing was evaluated from 30 min to 48 h by the measurement of electrical corneal resistance (CR) ratios. The cell viability decreased over time; the lowest values were observed with 1.5% levofloxacin. Significant differences in cell viability were observed among the 4 solutions at 72 h (P<0.05); the cell viabilities of 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin were 21.6%, 97.9%, 39.1%, and 67.5%, respectively. The electrical CR ratios at 48 h after instillation were 103.8% (saline), 78.2% (1.5% levofloxacin), 105.0% (0.5% levofloxacin), 74.9% (0.5% moxifloxacin), and 87.7% (0.3% gatifloxacin); the difference was significant between 1.5% levofloxacin or 0.5% moxifloxacin and saline (P<0.05). The cytotoxicities of 1.5% and 0.5% levofloxacin, 0.5% moxifloxacin, and 0.3% gatifloxacin were different, and 1.5% levofloxacin and 0.5% moxifloxacin resulted in delayed corneal wound healing. The results suggest that 1.5% levofloxacin exerts the greatest influence on corneal wound healing.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To explore the inhibitory effects of antivascular endothelial growth factor C (VEGF-C) therapy on corneal lymphangiogenesis and allograft rejection in rats. Fischer 344 rat corneas were transplanted into Lewis rat eyes. After corneal transplantation, Lewis rats (the recipients) were randomly and equally divided into 2 groups: anti-VEGF-C treatment (group A) and control (group B). Corneal hemangiogenesis and lymphangiogenesis were characterized using whole-mount immunofluorescence, and the immune rejection of the grafts was examined using a slit lamp and evaluated by scoring the rejection index (RI). In addition, the expression of VEGF-C was examined by immunohistochemistry and real-time polymerase chain reaction. The association of corneal lymphangiogenesis and hemangiogenesis with VEGF-C in transplanted corneas was also characterized. VEGF-C expression was markedly downregulated after anti-VEGF-C therapy. The outgrowth of corneal lymphangiogenesis dramatically decreased in group A. There was a significant relationship between VEGF-C reduction and the decrease in the lymphatic vessel area (r=0.55, P<0.05), whereas the relationship between the reduction of VEGF-C and the decrease in blood vessel area was not significant (r=0.11, P>0.05). In addition, the RI scores were significantly lower in group A compared with group B at 7, 10, and 14 days after transplantation. The graft survival time in group A rats (20.33±1.37 days) was significantly longer than that in group B rats (12.83±1.47 days; P<0.05). The results suggested that VEGF-C blockade had a significant role in preventing corneal lymphangiogenesis in corneal beds, which resulted in higher allograft survival rates.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: To evaluate the effects of oral methotrexate (MTX) in patients with chronic central serous chorioretinopathy (CSC). This is an interventional, prospective uncontrolled clinical trial, which included 23 eyes of 23 consecutive patients presenting with chronic symptomatic CSC and persistent subretinal fluid (SRF) for longer than 3 months. All patients were treated with 7.5 mg/week of oral MTX for 12 weeks. The best corrected visual acuity (BCVA), central macular thickness (CMT), SRF, and total macular volume recorded by monthly optical coherence tomography were analyzed. Complete blood count and serum liver enzymes level were monitored. Mean duration of CSC was 13 months (3-36 months). Mean BCVA improved from 20/40 at baseline to 20/30 at the third month and 20/28 at the sixth month (P=0.002 and 0.003, respectively). Mean CMT decreased from 375 μm at baseline to 278 μm and 265 μm at the third and sixth month (P=0.002 and 0.007, respectively). Mean total macular volume decreased from 9.33 mm(3) at baseline to 8.48 and 8.31 mm(3) at the third and sixth month (P=0.001 and 0.001, respectively). Thirteen (62%) eyes achieved complete resolution of SRF. No MTX-associated toxicity was detected. Low-dose oral MTX may be an alternative therapeutic option for the treatment of chronic CSC. This study paves the way for a randomized clinical trial comparing the effects of MTX treatment with photodynamic therapy or observation.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is the prototypical matricellular protein. Matricellular proteins are nonstructural secreted proteins that provide an integration between cells and their surrounding extracellular matrix (ECM). Regulation of the ECM is important in maintaining the physiologic function of tissues. Elevated levels of SPARC have been identified in a variety of diseases involving pathologic tissue remodeling, such as hepatic fibrosis, systemic sclerosis, and certain carcinomas. Within the eye, SPARC has been identified in the trabecular meshwork, lens, and retina. Studies have begun to show the role of SPARC in these tissues and its possible role, specifically in primary open-angle glaucoma, cataracts, and proliferative vitreoretinopathy. SPARC may, therefore, be a therapeutic target in the treatment of certain ocular diseases. Further investigation into the mechanism of action of SPARC will be necessary in the development of SPARC-targeted therapy.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that belongs to a family of evolutionary highly conserved calcium-binding proteins consisting of 5 members (TSP-1-TSP-5). In the eye, TSP-1 is expressed by several ocular cell types and is also detectable in the aqueous humor and the vitreous body. So far, TSP-1 is one of the major activators of TGFβ, suggesting a strong influence on various important cellular functions and interactions such as differentiation, migration, and wound healing. TSP-1 is also a key endogenous inhibitor of hem- and lymphangiogenesis. Several lines of evidence indicate a crucial role of TSP-1 in maintaining the ocular immune and angiogenic privilege, for example, by regulating T lymphocytes and the tolerance-promoting properties of ocular antigen-presenting cells. This review discusses the role of TSP-1 in dry eye disease and corneal graft rejection through its effects on hem- and lymphangiogenesis, as well as on the underlying immune responses. Recent work will be reviewed showing by which molecular mechanism TSP-1 modulates inflammatory processes during ocular diseases. This opens potential new treatment avenues in inflammatory and (lymph)angiogenic ocular diseases.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics
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    ABSTRACT: Increased expression of transforming growth factor-β2 (TGF-β2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-β2. Our aim was to compare the expression of molecules involved in TGF-β2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-β2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1(-/-)) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1β and both secreted protein and message levels of TSP-1, CD36, and TGF-β2 were analyzed. TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-β2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-β2 and CD36 conjunctival immunostaining was detected in TSP1(-/-) mice. The expression of TSP-1 and CD36 was downregulated in IL-1β-stimulated conjunctival fibroblasts at both the protein and message level, while active TGF-β2 was undetected. The absence or reduced expression of either of the molecules involved in TGF-β2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.
    No preview · Article · Jul 2015 · Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics