Safety, pharmacokinetics, and prevention effect of intraocular crocetin in proliferative vitreoretinopathy
| Autor: | Qingli Shang, Jianbin An, Caixia Wang, Jingxue Ma, Hai-Ting Chen, Hui-Fang Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Proliferative vitreoretinopathy genetic structures Crocetin PVR RM1-950 Retina Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Ophthalmology Electroretinography Medicine Animals Humans Vitamin A Pharmacology TUNEL assay Toxicity medicine.diagnostic_test business.industry Vitreoretinopathy Proliferative Fundus photography General Medicine medicine.disease Carotenoids eye diseases Disease Models Animal 030104 developmental biology chemistry 030220 oncology & carcinogenesis Intravitreal Injections Therapeutics. Pharmacology sense organs Rabbits HPLC business Erg Efficacy Study |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 109, Iss, Pp 1211-1220 (2019) |
| ISSN: | 1950-6007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect