Zinc Oxide Tetrapods Modulate Wound Healing and Cytokine Release In Vitro-A New Antiproliferative Substance in Glaucoma Filtering Surgery

氧化锌四足体体外调节伤口愈合和细胞因子释放——青光眼滤过手术中的一种新型抗增殖物质

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作者:Svenja Rebecca Sonntag, Stefanie Gniesmer, Anna Gapeeva, Rainer Adelung, Ala Cojocaru, Yogendra Kumar Mishra, Sören Kaps, Aysegül Tura, Swaantje Grisanti, Salvatore Grisanti, Khaled Nassar

Abstract

Glaucoma filtering surgery is applied to reduce intraocular pressure (IOP) in cases of uncontrolled glaucoma. However, postoperative fibrosis reduces the long-term success of both standard trabeculectomy and microstents. The aim of this study was to test the antiproliferative and anti-inflammatory potential of ZnO-tetrapods (ZnO-T) on human Tenon's fibroblasts (HTFs) for glaucoma surgery. The toxicity of ZnO-T on HTFs was determined using an MTT test. For analysis of fibroblast proliferation, migration, and transdifferentiation, cultures were stained for Ki67, alpha-smooth muscle actin (α-SMA), and p-SMAD. A fully quantitative multiplex ELISA was used to determine the concentrations of different cytokines, platelet-derived growth factor (PDGF), and hepatocyte growth factor (HGF) in culture supernatants with and without previous ZnO-T treatment. Treatment with higher concentrations (10 and 20 µg/mL) was associated with HTF toxicity, as shown in the wound healing assay. Furthermore, the number of Ki67, α-SMA-positive, and pSMAD-positive cells, as well as IL-6 and HGF in supernatants, were significantly reduced following incubation with ZnO-T. In conclusion, we were able to show the antiproliferative and anti-inflammatory potentials of ZnO-T. Therefore, the use of ZnO-T may provide a new approach to reducing postoperative fibrosis in glaucoma filtering surgery.

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