Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14174, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Noor Ophthalmology Research Center, Noor Eye hospital, Tehran, Iran.
Carbohydr Polym. 2018 Jan 1;179:42-49. doi: 10.1016/j.carbpol.2017.09.062. Epub 2017 Sep 21.
Corneal haze, commonly caused by deep physical and chemical injuries, can greatly impair vision. Growth factors facilitate fibroblast proliferation and differentiation, which leads to haze intensity. In this study, the potential effect of chitosan (CS) and thiolated-chitosan (TCS) nanoparticles and solutions on inhibition of fibroblast proliferation, fibroblast to myofibroblast differentiation, neovascularization, extracellular matrix (ECM) deposition, and pro-fibrotic cytokine expression was examined. Transforming growth factor beta-1 (TGFβ) was induced by interleukin-6 (IL6) in human corneal fibroblasts and expression levels of TGFβ, Platelet-derived growth factor (PDGF), α-smooth muscle actins (α-SMA), collagen type I (Col I), fibronectin (Fn) and vascular endothelial growth factor (VEGF) were quantified using qRT-PCR. To assess wound-healing capacity, TCS-treated mice were examined for α-SMA positive cells, collagen deposition, inflammatory cells and neovascularization through pathological immunohistochemistry. The results revealed that CS and TCS could down-regulate the expression levels of TGFβ and PDGF comparable to that of TGFβ knockdown experiment. However, down-regulation of TGFβ was not regulated through miR29b induction. Neovascularization along with α-SMA and ECM deposition were significantly diminished. According to these findings, CS and TCS can be considered as potential anti-fibrotic and anti-angiogenic therapeutics. Furthermore, TCS, thiolated derivative of CS, will increase mucoadhesion of the polymer at the corneal surface which makes the polymer efficient and non-toxic therapeutic approach for corneal injuries.
角膜混浊，通常由深度物理和化学损伤引起，会极大地损害视力。生长因子促进成纤维细胞增殖和分化，导致混浊强度增加。在这项研究中，研究了壳聚糖（CS）和巯基化壳聚糖（TCS）纳米粒子和溶液对抑制成纤维细胞增殖、成纤维细胞向肌成纤维细胞分化、新生血管形成、细胞外基质（ECM）沉积和促纤维化细胞因子表达的潜在作用。转化生长因子β-1（TGFβ）由白细胞介素 6（IL6）诱导人角膜成纤维细胞，并使用 qRT-PCR 定量测定 TGFβ、血小板衍生生长因子（PDGF）、α-平滑肌肌动蛋白（α-SMA）、胶原 I（Col I）、纤维连接蛋白（Fn）和血管内皮生长因子（VEGF）的表达水平。为了评估伤口愈合能力，通过病理免疫组织化学检查 TCS 处理的小鼠中 α-SMA 阳性细胞、胶原沉积、炎症细胞和新生血管形成。结果表明，CS 和 TCS 可以下调 TGFβ和 PDGF 的表达水平，与 TGFβ 敲低实验相当。然而，TGFβ 的下调不是通过 miR29b 诱导来调节的。新生血管形成以及α-SMA 和 ECM 沉积显著减少。根据这些发现，CS 和 TCS 可以被认为是潜在的抗纤维化和抗血管生成治疗方法。此外，CS 的巯基化衍生物 TCS 将增加聚合物在角膜表面的粘膜粘附性，使聚合物成为治疗角膜损伤的有效且无毒的治疗方法。
