کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6196819 1602595 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast
چکیده انگلیسی


- This study aims to understand effects of ranibizumab on extracellular matrix component.
- Analysis of gene and protein expression was done using PCR and ELISA techniques.
- Ranibizumab inhibits collagen type 1 alpha 1 mRNA but increase its protein accumulation.
- Ranibizumab caused insignificant impact on fibronectin mRNA and increase its protein accumulation.
- We demonstrated that ranibizumab would be a potential anti-scarring agent in trabeculectomy.

Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p < 0.05). Ranibizumab caused significant reduction of collagen type 1 alpha 1 (COL1A1) mRNA, but not for fibronectin (FN). Meanwhile, COL1A1 and FN protein levels were found upregulated in treated monolayers compared to control monolayers. Ranibizumab at 0.5 mg/mL significantly reduced cell viability in cultured HTF. From this study, we found that single application of ranibizumab is inadequate to induce the anti-fibrotic effects on HTF, suggesting the importance of adjunctive therapy. Further studies are underway to understand mechanism of actions of ranibizumab on HTF.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 127, October 2014, Pages 236-242
نویسندگان
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