Résumé
PURPOSE: To evaluate the inhibitory effect of tranilast on the formation of posterior capsular opacity (PCO) after a cataract operation ex vivo and in a rabbit model. METHODS: A human lens epithelial cell line (B3) was treated with 0.005-0.1 mM tranilast. Cytotoxicity assessment and effective dosage determination of tranilast were performed using MTT assays. B3 cell lines were cultured in Eagle's minimal essential medium (EMEM) containing 20% FBS with different concentrationsof tranilast, and morphological differences were observed. To investigate the effect of tranilast on cytokine production in B3 cell lines, cells were treated with 0.01 mM tranilast and expression profiles of cytokines were analyzed by RT-PCR. After performing phacoemulsification and intraocular lens implantation in 10 white rabbits, 0.5% tranilast eye drops were given 4 times per day, and the severity of PCO was evaluated bi-weekly using POCOman for 8 weeks after the operation. RESULTS: Cell death was observed in the 0.05 mM tranilast-treated B3 cell lines, and inhibition of epithelial-mesenchymal transition (EMT) was also observed in the 0.01 mM tranilast-treated B3 cell lines. TGF-beta1/2, IL-18, and CDK7 mRNA expression decreased in the 0.01 mM tranilast-treated B3 cell lines. Significant suppression of PCO formation was observed in rabbits treated with 0.5% tranilast eye drops 5 weeks post operative (p<0.05). CONCLUSIONS: The results from this study show that tranilast suppresses EMT through inhibition of TGF-beta, IL-18,and CDK7 expression. The results suggest that tranilast can be used toprevent PCO formation after cataract surgery.
Sujets)
Humains , Lapins , Cataracte , Mort cellulaire , Lignée cellulaire , Cytokines , Cellules épithéliales , Transition épithélio-mésenchymateuse , Interleukine-18 , Pose d'implant intraoculaire , Solutions ophtalmiques , ortho-Aminobenzoates , Phacoémulsification , ARN messager , Facteur de croissance transformant bêtaRésumé
PURPOSE: To evaluate the inhibitory effect of tranilast on the formation of posterior capsular opacity (PCO) after a cataract operation ex vivo and in a rabbit model. METHODS: A human lens epithelial cell line (B3) was treated with 0.005-0.1 mM tranilast. Cytotoxicity assessment and effective dosage determination of tranilast were performed using MTT assays. B3 cell lines were cultured in Eagle's minimal essential medium (EMEM) containing 20% FBS with different concentrationsof tranilast, and morphological differences were observed. To investigate the effect of tranilast on cytokine production in B3 cell lines, cells were treated with 0.01 mM tranilast and expression profiles of cytokines were analyzed by RT-PCR. After performing phacoemulsification and intraocular lens implantation in 10 white rabbits, 0.5% tranilast eye drops were given 4 times per day, and the severity of PCO was evaluated bi-weekly using POCOman for 8 weeks after the operation. RESULTS: Cell death was observed in the 0.05 mM tranilast-treated B3 cell lines, and inhibition of epithelial-mesenchymal transition (EMT) was also observed in the 0.01 mM tranilast-treated B3 cell lines. TGF-beta1/2, IL-18, and CDK7 mRNA expression decreased in the 0.01 mM tranilast-treated B3 cell lines. Significant suppression of PCO formation was observed in rabbits treated with 0.5% tranilast eye drops 5 weeks post operative (p<0.05). CONCLUSIONS: The results from this study show that tranilast suppresses EMT through inhibition of TGF-beta, IL-18,and CDK7 expression. The results suggest that tranilast can be used toprevent PCO formation after cataract surgery.