Department of Ophthalmology, The Second Hospital of HeBei Medical University, Shijiazhuang, 050000, China; Department of Ophthalmology, Shijiazhuang Aier Eye Hospital, Shijiazhuang, 050000, China.
Department of Ophthalmology, The Second Hospital of HeBei Medical University, Shijiazhuang, 050000, China.
Biomed Pharmacother. 2019 Jan;109:1211-1220. doi: 10.1016/j.biopha.2018.10.193. Epub 2018 Nov 7.
The study was designed to determine the safety and pharmacokinetics of intraocular crocetin and examine whether crocetin inhibits the development of proliferative vitreoretinopathy (PVR) in a rabbit model. In the toxicity study, the right eyes of rabbits were injected with 0.2 μmol or 0.4 μmol crocetin. The left eyes were injected with 0.1 ml phosphate buffered saline (PBS) containing the same concentration of DMSO. Fundus photography, optical coherence tomography (OCT), and electroretinogram (ERG) were obtained at baseline and 14 days. Afterward, the eyes were enucleated for histopathological analysis and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay. In the pharmacokinetic study, the eyes received an intravitreous injection of 0.4 μmol crocetin to detect vitreous drug levels with HPLC at specific time points. In the efficacy study, PVR was induced with an intravitreal injection of ARPE-19 cells in rabbits. Then ten eyes were injected with 0.4 μmol crocetin, and the other 10 eyes received 0.1 ml PBS. Fundus photography, OCT and ERG were performed at days 3 and 7 and weekly for a total of 4 weeks after injection. Afterward, the eyes were enucleated and subjected to histological analysis and TUNEL staining. The results demonstrated no signs of retinal toxicity. Intravitreal injection of 0.4 μmol crocetin had a half-life of 4.231 h. Treatment with crocetin significantly inhibited the progression of PVR in parallel with a reduced expression of α-SMA, collagen fibers and Ki67. These results indicate that crocetin is an effective and safe inhibitor of PVR in rabbit models.
这项研究旨在确定眼内crocin 的安全性和药代动力学，并研究 crocin 是否能抑制兔眼增生性玻璃体视网膜病变（PVR）的发展。在毒性研究中，将 0.2μmol 或 0.4μmol crocin 注入兔子的右眼，左眼注射相同浓度 DMSO 的磷酸盐缓冲盐水（PBS）0.1ml。在基线和第 14 天，分别进行眼底照相、光学相干断层扫描（OCT）和视网膜电图（ERG）检查。之后，眼球摘出进行组织病理学分析和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）检测。在药代动力学研究中，通过 HPLC 检测特定时间点玻璃体内药物浓度，对右眼进行 0.4μmol crocin 玻璃体腔内注射。在疗效研究中，用 ARPE-19 细胞玻璃体腔注射诱导兔 PVR，其中 10 只眼注射 0.4μmol crocin，另 10 只眼注射 0.1ml PBS。注射后第 3 天和第 7 天，每周进行一次眼底照相、OCT 和 ERG 检查，共 4 周。之后眼球摘出，进行组织学分析和 TUNEL 染色。结果表明视网膜无毒性迹象。玻璃体腔内注射 0.4μmol crocin 的半衰期为 4.231h。crocin 治疗可显著抑制 PVR 的进展，同时α-SMA、胶原纤维和 Ki67 的表达减少。这些结果表明，crocin 是兔 PVR 模型中有效且安全的抑制剂。
