兔眼玻璃体腔植入维甲酸缓释系统防治增殖性玻璃体视网膜病变的药效学研究

目的　探讨全反式维甲酸 (atRA)缓释系统玻璃体腔植入对实验性增殖性玻璃体视网膜病变 (PVR)的预防作用。方法　采用中轴部玻璃体切除联合成纤维细胞注入术构建兔PVR模型。术中 3组兔眼玻璃体腔均分别植入不同含量的atRA缓释系统 :B组缓释系统atRA含量为 42 0 μg ,C组缓释系统atRA含量为 650 μg ,D组缓释系统atRA含量为 1 0 70 μg ;设空白对照两组 :A组不植入atRA缓释系统 ,E组玻璃体腔植入空白atRA缓释系统。植入后共观察 8周 ,每周抽取玻璃体腔液进行atRA含量检测。 8周后行组织病理学检查。结果　术后 8周 ,植入atRA含量 650 μg和 1 0 70 μg缓释系统组 ,兔眼PVR程度低于其他各组 ,经统计学分析差异有显著意义 (P <0 0 5) ,组织病理学检查未见眼内毒性反应。结论　atRA缓释系统玻璃体腔给药方便、安全。atRA抑制PVR能力与玻璃体腔药物浓度相关 ,atRA含量为 650 μg和 1 0 70 μg缓释系统植入玻璃体腔可有效预防术后PVR发生 ,而atRA含量为 42 0 μg缓释系统植入玻璃体腔仅能抑制和延缓PVR发生

Antiproliferative effect of sustained drug delivery system of all-trans retinoic acid implant into rabbit's vitreous cavity for treatment of proliferative vitreoretinopathy

OBJECTIVE: To investigate the antiproliferative effect of different concentration of all-trans retinoic acid (atRA) in a drug delivery system (DDS) in an experimental proliferative vitreoretinopathy (PVR) model. METHODS: The PVR animal model was induced by central vitrectomy and homologous fibroblasts injected at the same time in pigmented rabbits. Fifty rabbits underwent the surgery. These rabbits were divided into 5 groups of 10 rabbits at random. Group A was the control group. In group B, C, and E, one DDS device was implanted into the vitreous cavity after the vitrectomy, each DDS contained atRA 420 microg, 650 microg and no drug, respectively. In group D, two DDS devices were placed into the vitreous cavity, the total atRA content was 1,070 microg (420 microg + 650 microg). Each group was observed for 8 weeks. The development and the severity of PVR were observed and recorded. The vitreous cavity fluid was aspirated each week for measurement of the concentration of the atRA, in order to estimate the relationship between PVR and concentration of atRA. After 8 weeks, the retinal toxicity was evaluated by histopathology. Statistical analyses were performed at the end of the experiment. RESULTS: Eight weeks after the operation, the incidence of PVR was lower in group C and group D, and there was a significantly statistical difference between these two groups and other groups. No intraocular toxicity was found by the histopathology examination. CONCLUSIONS: atRA DDS is a safe and convenient mode for intraocular administration. DDS containing 650 microg and 1,070 microg atRA can inhibit the cell proliferation in the vitreous cavity effectively after surgery. atRA at a lower concentration cannot eliminate the cell proliferation but may delay the occurrence of PVR.