Abstract
Abstract Implants that feature a drug delivery system loaded with antifibrotic active drugs provide a promising approach to address postoperative complications caused by fibrosis. This study is intended to clarify whether Actinomycin D has an impact specifically on components of the extracellular matrix (ECM) and its formation in human primary fibroblasts of the Tenon capsule (hTF). Furthermore, the suitability of this agent in poly(N-vinylpyrrolidone)- poly(methylmethacrylate)(PVP-co-PMMA) as a drug delivery model is evaluated in drug incorporation and release studies. RT-qPCR revealed a significant downregulation of the fibrotic marker genes ACTA2, COL1A1 and FN1 in cells stimulated with TGF- β1 and additionally treated with Actinomycin D. However, these findings could only be confirmed on α- SMA protein level. collagen I and Fibronectin synthesis stayed unaffected. The diffusion based incorporation of Actinomycin D into the polymer model proved to be very effective. The release of the agent was retarded with a slightly prolonged kinetic. These findings make Actinomycin D a promising antifibrotic agent in ophthalmic implant surgery.
Highlights
In ophthalmic implant surgery, fibrosis is still one of the main causes for postoperative complications
For cell culture experiments Actinomycin D stock solution was further diluted in Dulbecco's Modified Eagle Medium (DMEM) and used in a concentration of 10 nM
There were four different treatment groups, DMEM with 10 nM Actinomycin D, with 10 ng/mL TGF, with both 10 nM Actinomycin D and 10 ng/mL TGF- Pure DMEM was used as control group
Summary
Fibrosis is still one of the main causes for postoperative complications. Actinomycin D has been used as an anti-tumor drug in clinical practice since 1954 It exerts its anti-tumour activity by inhibiting protein biosynthesis through an intervention in mRNA synthesis [5]. Fibronectins are cell surface glycoproteins interacting with diverse ECM proteins like collagen, fibrin and integrin [11]. It has recently been shown, that secretion of these ECM factors was strongly induced in TGF- 1 stimulated hTFs [12]. A. Brietzke et al, Actinomycin D for fibrosis management in ophthalmic implant surgery — 482
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