Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
PLoS One. 2023 Apr 20;18(4):e0284618. doi: 10.1371/journal.pone.0284618. eCollection 2023.
To investigate the inhibitory effect of a hyaluronic acid hydrogel loaded with hydroxycamptothecin (HCPT) on scar formation after filtration surgery in a rabbit model.
Scleral fibroblasts were isolated and extracted from rabbits' eyes. After treatment with different concentrations of HCPT, cytotoxicity was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and proliferation and extent of apoptosis were analysed using flow cytometry. Hydrogels loaded with different dosages of HCPT were prepared and placed under the scleral flap after the filtration surgery. One day, one week, and two weeks after surgery, follicular, conjunctival, corneal, and anterior chamber inflammation and iris and lens changes were observed.
In vitro, compared with cells not treated with HCPT, cells treated with HCPT had decreased survival rate and proliferation, and the apoptosis level increased with increasing HCPT concentrations (p < 0.05). In vivo, the flattening time of filtering blebs in the three groups treated with different dosages of HCPT hydrogel was delayed. The degrees of oedema, inflammation, and bleeding were similar to those observed in the control group. The HCPT hydrogel effectively downregulated the expression of collagen 1 and 3 and tissue inhibitor of metalloproteinase 2 and upregulated the expression of matrix metalloproteinase 2 in a dose-dependent manner.
HCPT significantly inhibited the growth of rabbits' scleral fibroblasts and effectively inhibited scar formation after filtering surgery by accelerating the degradation of extracellular matrix deposition.
研究载羟基喜树碱（HCPT）透明质酸水凝胶对兔滤过性手术后排异反应的抑制作用。
分离并提取兔眼巩膜成纤维细胞。用不同浓度的 HCPT 处理后，用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法检测细胞毒性，并用流式细胞术分析细胞增殖和凋亡程度。制备载不同剂量 HCPT 的水凝胶，并在滤过性手术后置于巩膜瓣下。术后 1d、1 周和 2 周，观察滤泡、结膜、角膜和前房炎症以及虹膜和晶状体变化。
体外实验中，与未用 HCPT 处理的细胞相比，用 HCPT 处理的细胞存活率和增殖率降低，凋亡水平随 HCPT 浓度增加而增加（p < 0.05）。体内实验中，载不同剂量 HCPT 水凝胶治疗组滤过泡扁平时间延迟。水肿、炎症和出血程度与对照组相似。HCPT 水凝胶能有效下调胶原 1 和 3 及金属蛋白酶组织抑制剂 2 的表达，并呈剂量依赖性上调基质金属蛋白酶 2 的表达。
HCPT 能显著抑制兔巩膜成纤维细胞的生长，通过加速细胞外基质沉积的降解，有效抑制滤过性手术后的瘢痕形成。
