Anti-conglutination Effect of Apc0576 on Human Tenon’s Capsule Fibroblasts in vitro

Abstract

Abstract: : Purpose: After glaucoma surgery such as trabeculectomy, it is important to prevent inflammation which causes scar formation to control intraocular pressure for a long period. So, Various pharmacologic agents have been tested in attempts to prevent scar formation. Using human Tenon’s capsular fibroblasts (TCF) in vitro, we examined the effects of APC0576, which suppresses NF-ΚB-dependent gene activation of human vascular endothelial cells without adversely affecting cell viability. Methods: Human TCF were cultured from the patients who received conjunctival chalasis resection. The effects of APC0576 (0 - 30 µg/ml) were compared with vehicle control. IL-8 and MCP-1 production after IL-1α stimulation was detected in supernatants by standardized ELISA assay with or without APC0576. After TGF-ß (10ng/ml) stimulation, extracellular matrix (ECM) proteins; type I procollagen (PIP), fibronectin (FN) and laminin (LN), were also detected in both supernatants and cell lysates by ELISA assay. Finally, TCF proliferation responses with IL-1α stimulation were assayed with or without APC0576. Results: In comparison with vehicle control, APC0576 (10 µg/ml) significantly suppressed IL-8 (to 67%; p<0.01) and MCP-1 production (to 49%; p<0.01). APC0576 (30 µg/ml) significantly suppressed PIP production (supernatants: 31%, p<0.01; cell lysates: 39%, p<0.001), FN (cell lysates: 36%, p<0.01), and LN (supernatants: 44%, p<0.05; cell lysates: 21%, p<0.05). IL-1α-induced TCF proliferation was significantly inhibited (62%, p<0.01) by APC0576 of 10 µg/ml. Conclusions: APC0576 inhibited proinflammatory chemokine production with IL-1α stimulation and TGF-ß induced ECM production. TCF proliferation was also inhibited. We conclude that APC0576 can suppress both postoperative inflammation and scar formation, and therefore may eventually be a novel therapeutic candidate for management after trabeculectomy.

Keywords: wound healing • cytokines/chemokines • proliferation