维甲酸缓释系统抑制兔眼滤过术后瘢痕形成的效果研究

Experimental study on the effect of Retinoic Acid Drug Delivery System in Glaucoma Filtration surgery in rabbits

目的研究维甲酸缓释系统（retinoic aciddmgdelivery system，RADDS）抑制兔眼滤过手术后瘢痕形成的有效性和可行性。方法①随机选择新西兰大白兔25只，兔龄为12～14周，体重2~2．5kg，双眼均施以小梁切除术。所有兔左眼均放置RADDS，为RA＋PLGA组。右眼随机选择15只眼仅放置缓释药膜，为PLGA组。10只眼作为空白对照，仅作单纯的小梁切除术，为NV组。②术后观察兔眼前房、眼睑、结膜及角膜的毒性反应，以判定兔眼对RADDS的耐受性。③通过滤过泡的面积、眼内压观察RADDS对滤过手术效果的影响。④术后第7、14、30、60、90d时分批处死兔子，摘除眼球对手术部位行组织病理学检查。结果（1）兔眼对RADDS表现出良好的耐受性，所有手术眼均未出现眼内炎症以及眼睑、结膜及角膜的毒性反应。（2）RADDS显著提高了兔眼滤过性手术的效果，RA＋PLGA组滤过泡的生存时间与PLGA组及NV组相比显著延长（10grank检验，P〈0．001）。与PLGA组及NV组相比，RA＋PLGA组眼内压维持了较长时间的低眼压水平（P〈0．001）。（3）Weigert和VanGieson结缔组织特殊染色显示RA＋PLGA组滤过道部位结膜上皮下弹力纤维及胶原纤维等瘢痕组织的形成明显受到抑制（方差分析，P〈0．01）。结论RADDS提高了滤过手术的效果且局部的毒副反应小，有望成为一种安全、有效且使用方便的抗青光眼术后瘢痕形成的治疗方法。

Objective To investigate the efficacy and feasibility ofretinoic acid drug delivery system as glaucoma anti-scarring agent by observing its effect on a rabbit model of glaucoma filtration surgery. Methods （1）Filtering surgery was performed in both eyes of 25 New Zealand white rabbits, weighing 2 to 2.5 kg and aged 12 to 14 weeks. The all left eyes received RA DDS, 15 right eyes only received DDS randomly; the remaining 10 right eyes were null vehicle. （2）Tolerance and safety ofRA DDS were investigated by assessment of local toxicity, using clinical parameters such as anterior chamber activity, lid edema, chemosis, hemorrhage, and corneal toxicity. （3）Effeets in filtering surgery of RA DDS were evaluated by observations of the bleb area, and IOP. （4）The rabbits were killed on days 7,14,30,60 and 90 after surgery. Both eyes were enucleated and histologically analyzed to observe the extracellular matrix components in surgery site. Results Placements ofRA DDS in surgery sites were well tolerated in surgery eyes of New Zealand White rabbits. No intraoeular inflammation was seen in any rabbit at any time in the study, as well as lid edema, chemosis, hemorrlaage, and corneal toxicity. （2）RA DDS was associated with successful filtration surgery, evidenced by bleb morphology（log rank, P 〈0.001 ）. Compared with PLGA group and NV group, the IOP remained consistently lower than baseline measurements in the RA＋PLGA group （P 〈 0.001 ）. （3）Total scar formation and architec-ture in the subconjunctival areas at the filtration site, judged by staining characteristics with Weigert and Van Gieson, was significantly reduced in RA＋PLGA group compared with control treatments （P 〈 0.01, ANO- VA）. Conclusions RA DDS was found to improve glaucoma filtration surgery outcome significantly without toxicity and side-effect. It has potential as a safe and effective anti-scarring agent for easy use in glaucoma illtration surgery.