Metformin Reduced Collagen Deposition and Contractility, but Increased Collagen Degradation in in vitro Posterior Capsule Opacification Model

Abstract

BACKGROUND: Posterior capsule opacification (PCO) often occurs after cataract surgery. Metformin has been known to have an ability to inhibit fibrosis. This study aimed to investigate the effects of metformin on cell contractility, collagen deposition and degradation in human lens epithelial cells (HLEC) of cataract patients.METHODS: HLEC were isolated from the anterior lens capsule of patients undergoing cataract surgery. The HLEC culture was carried out using explant culture technique. The in vitro PCO model was created by scratching technique on HLEC cultures. The treatment groups were given 0.1, 0.5 and 1 mM metformin, respectively, while the control group were given 10% fetal bovine serum (FBS). On the 7th day after scratching technique, the collagen deposition, collagen degradation and cell contractility were evaluated.RESULTS: Collagen deposition in HLEC was significantly reduced after given 0.1 mM, 0.5 mM and 1 mM metformin (17.92±6.16 mg/mL, 12.92±4.31 mg/mL, 11.25±5.30 mg/mL, respectively), compared to the control group (31.46±7.52 μg/mL, p=0.002). Collagen degradation significantly was increased in the 0.1 mM, 0.5 mM and 1 mM metformin groups (4.77±9.27 mg/mL, 6.59±1.16 mg/mL, 6.35±1.90 mg/mL, respectively) compared to the control group (2.21±2.78 μg/mL, p=0.002). While, collagen contractility in HLEC was significantly reduced in 0.1mM, 0.5mM and 1 mM metformin groups (16.39±3.89%, 13.89±2.59%, 11.93±2.44%, respectively), compared to the control group (44.25±4.95%, p=0.000).CONCLUSION: Metformin reduced collagen deposition and contractility, but increased collagen degradation in HLEC of cataract patients through mechanism of extracellular matrix remodeling.KEYWORDS: metformin, human lens epithelial cell, fibrosis

Hubungan Derajat Katarak Dan Durasi Diabetes Melitus Tipe 2 Di Instalasi Rawat Jalan Mata Rsud Dr. Soetomo Surabaya

“…PCO dapat disebabkan oleh operasi katarak yang dikombinasikan dengan reaksi peradangan yang disebabkan oleh benda asing seperti lensa intraokular. Sel epitel lensa (LECs) yang tersisa di kapsul lensa anterior selama operasi katarak akan mengalami proliferasi, migrasi dan trans-differensi ke kapsul posterior yang akan memicu fibrosis dan akhirnya menjadi PCO (Brilliyanto et al, 2021). Angka kejadian PCO cukup tinggi sebesar 40% setelah implantasi lensa intraokular ekstraksi katarak terutama pada pasien dengan faktor risiko uveitis dan diabetes (Trianggadewi et al, 2019).…”

Matrix Metalloproteinase-3 Down Regulation and Cell Migration Inhibition in Human Pterygium Fibroblasts by Mitomycin-C, Curcumin and Fibrin Glue

“…This occurs most probably due to the suppressing effect of the mediators including TGF-β, MMP and other profibrotic mediators via the NF-κB through tumor necrosis factor (TNF)-a dependent induction and mitogen-activated protein kinase (MAPK) signaling pathway. (20,23,24) FG significantly inhibits collagen synthesis and induces collagen degradation in human tenons, in which the wound healing manner is regulated by inflammation. A decrease in the amount of collagen will eliminate the antiinflammatory response and fibrin glue substantially inhibits collagen in the injured tenon model and is able to reduce wound formation and contractures.…”