曲安奈德缓释剂植入脉络膜上腔防治外伤性前部增生性玻璃体视网膜病变

Implantation of a triamcinolone acetonide drug delivery system into the suprachoroidal space for the prevention of traumatic anterior proliferative vitreoretinopathy

背景前部增生性玻璃体视网膜病变（aPVR）是多种细胞参与的损伤修复过程，目前临床尚无常规应用于防治aPVR的药物。壳聚糖是一种新型的缓释给药载体，载药量大，药物作用时间长，成为近年来研究的热点。目的比较壳聚糖缓释给药系统植入脉络膜上腔与玻璃体腔注射曲安奈德（TA）防治外伤性aPVR的疗效。方法75只健康青紫蓝兔，应用随机数字表法随机分为空白对照组、TA＋壳聚糖组、TA注射组、模型对照组、正常对照组，每组15只兔（15只眼）。除正常对照组外，其他各组于兔左眼距角膜缘2．5mm处10：30～11：30位制作长为5mm的巩膜穿孔伤，并用11号手术尖刀穿刺深约10mm，用刀轻划兔眼虹膜睫状体部制作外伤性aPVR模型，空白对照组在脉络膜上腔植入空白壳聚糖，TA＋壳聚糖组在脉络膜上腔植入壳聚糖缓释给药系统（载药1mgTA），TA注射组在玻璃体腔注射TA溶液（含1mgTA），模型对照组仅制作外伤模型。分别于术后2、5、8周利用超声生物显微镜（UBM）观察各组睫状体增厚程度以及有无增生膜形成；术后8周过量麻醉法处死动物并制作眼部组织标本，行组织病理学检查和超微结构观察。结果组织学检查表明，实验后8周空白对照组、TA注射组、模型对照组兔睫状体组织均明显水肿，可见炎性细胞浸润，TA＋壳聚糖组兔睫状体组织水肿较轻。电子显微镜下空白对照组、模型对照组兔睫状体组织细胞器明显损伤，TA＋壳聚糖组损伤减轻。UBM检查显示TA＋壳聚糖组兔睫状体组织及虹膜为轻度异常，而空白对照组、TA注射组、模型对照组可见明显异常。术后2、5、8周，5个组睫状体厚度值的比较差异均有统计学意义（F=212．938、515．323、447．919，P〈0．01）。与正常对照组相比，各时间点空白对照组、模型对照组、TA注射组兔睫状体组织均增厚，差异均有统计学意义（P〈0．05），而TA＋壳聚糖组睫状体厚度值接近正常对照组（2周：0．484±0．075VS．0．327±0．094；5周：0．422±0．089VS．0．327±0．094；8周：0．418±0．085VS．0．327±0．094）．萃异均无统计学意义（P〉0．05）。结论载药TA壳聚糖缓释给药系统能够抑制虹膜、睫状体等的增生，防治外伤性aPVR的形成。

Background Anterior proliferative vitreoretinopathy （aPVR） is a tissue injury and repair progress,and treatment of aPVR is very important in clinic. Chitosan drug delivery system is becoming a hot spot for its large lading dose and long acting duration. Objective The present study was to investigate the curative effect of a triamcinolone acetonide （TA） drug delivery system after implantation into the suprachoroidal space to treat traumatic aPVR. Methods aPVR models were created in the left eyes of 65 healthy pigment rabbits by performing a 5 mm penetrating incision 2, 5 mm posterior to limbum at 10：30-11：30. The animals were randomly divided into 4 groups. Blank chitosan was implanted into the suprachoroidal space as the blank control group. Chitosan with 1 mg TA was implanted in the TA ± chitosa group. The TA solution （containing 1 mg TA） was intravitreally injected in the TA injection group. Fifteen models were used as the traumatic control group. Another 15 left eyes of normal pigment rabbits were used as the normal control group. The thickness of the ciliary tissue was measured using a ultrasound biomieroscope （UBM） 3,5 and 8 weeks after operation. The animals were sacrificed by excessive anesthesia and eyeballs were obtained for histopathologieal and ultrastructural examinations. Results Histopathological examination showed the edema of the ciliary tissue and inflammatory cells infiltration in the blank control group,TA injection group and model control group,but mild response was seen in the TA ± chitosa group. Severe damage in the ciliary tissue and subcellular organelle was found in the blank and model control groups, but mild damage was detected in the TA ± chitosa group under the transmission electron microscope. UBM examination revealed that obvious abnormalities were visible in the ciliary and iris tissue in the blank control group,TA injection group and traumatic control group,but a mild abnormality was seen in the TA ± ehitosa group. Significant differences in ciliary thickness were exhibited among the 5 groups 2,5 and 8 weeks after operation （ F = 212. 938,515. 323,447. 919, P 〈 0.01 ）. Compared with the normal control group, ciliary thickness significantly increased in the blank control group and normal control group at various time points （all P〈0. 05） ,but that in the TA ± ehitosa group was significantly lower than the normal control group at various time points （ two weeks：0. 484±0. 075 vs. 0. 327±0. 094;five weeks：0. 422±0. 089 vs. 0. 327±0. 094 ;eight weeks ：0. 418±0. 085 vs. 0. 327±0. 094） （ all P〉0.05 ）. Conclusions The ehitosan drug delivery system with TA suppresses the excessive proliferation of injured ocular tissue after implantation into the suprachoroidal space,which prevents the formation and development of aPVR.