Diclofenac Protects Cultured Human Corneal Epithelial Cells Against Hyperosmolarity and Ameliorates Corneal Surface Damage in a Rat Model of Dry Eye

Sawazaki, Ryoichi; Ishihara, Takeshi; Usui, Shinya; Hayashi, Erika; Tahara, Kayoko; Hoshino, Tatsuya; Higuchi, Akon; Nakamura, Shigeru; Tsubota, Kazuo; Mizushima, Tohru

doi:10.1167/iovs.13-13850

Cited by 33 publications

(26 citation statements)

References 36 publications

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“…7d . Experimental induction of DED could trigger a large amount of apoptotic cells in rabbit corneal epithelium, which corresponds with those found in other animal studies using mice 24 or rats 25 . In both Ctrl and EGCG groups, significant increases in the number of TUNEL-positive cells were found compared to the values of the DED groups ( P < 0.05).…”

Section: Resultssupporting

confidence: 89%

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome

Luo

Lai

2017

Sci Rep

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Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop gelatin-g-poly(N-isopropylacrylamide) (GN) carriers for topical epigallocatechin gallate (EGCG) administration in the treatment of dry eye disease (DED). By temperature triggered sol-gel phase transition of copolymers, EGCG-loaded GN was prepared at 32 °C and characterized by FTIR, NMR, and HPLC analyses. Results of WST-1 and live/dead assays showed that GN materials have good compatibility with corneal epithelial cells. Gradual biodegradation of delivery carriers allowed sustained release of EGCG without drug toxicity. Anti-inflammatory and antioxidant activity studies also indicated effective therapeutic drug levels at each time point within 3 days of release. In a rabbit dry eye model, corneal epithelial defects was ameliorated by treatment with single-dose administration of EGCG-containing GN. Furthermore, drug molecules released from carrier materials could prevent further tear evaporation and loss of mucin-secreting goblet cells in diseased animals. Our findings suggest that GN carrier is responsible for enhanced pharmacological efficacy of topically instilled EGCG, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form.

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Section: Resultssupporting

confidence: 89%

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome

Luo

Lai

2017

Sci Rep

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“…All cells were cultured in a humidified atmosphere of 95% air with 5% CO 2 at 37 °C. Viable cell number was monitored by MTT method 38 . Amounts of collagen in culture media were measured with a Sircol™ Collagen assay kit according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice

Tanaka

Niino

Ishihara

et al. 2017

Sci Rep

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Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca2+ channel blocker that has been used clinically to treat patients with high blood pressure. Felodipine suppressed collagen production within LL29 cells in the presence of TGF-β1, but not in its absence. Intratracheal administration of felodipine prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction. Felodipine also improved pulmonary fibrosis, as well as lung and respiratory function when administered after fibrosis development. Furthermore, administration of felodipine suppressed a bleomycin-induced increase in activated fibroblasts in the lung. We also found other dihydropyridine Ca2+ channel blockers (nifedipine and benidipine) inhibited collagen production in vitro and partially prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction in vivo. We propose that these Ca2+ channel blockers may be therapeutically beneficial for IPF patients.

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“…63 Given these clinical and preclinical findings, our results suggest nonsteroidal antiinflammatory drugs that target prostaglandin synthesis may alleviate inflammation in dry eye disease. 64 …”

Section: Journal Of Proteome Researchmentioning

confidence: 99%

Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress

Chen

Guo

et al. 2015

J. Proteome Res.

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"Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms. This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC, as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. Global and targeted metabonomic analyses as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 (control), 380, and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared with controls. SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment.

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Diclofenac Protects Cultured Human Corneal Epithelial Cells Against Hyperosmolarity and Ameliorates Corneal Surface Damage in a Rat Model of Dry Eye

Cited by 33 publications

References 36 publications

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome

Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice

Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress

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