Anti-scarring effects of triamcinolone acetonide/polylactic acid caprolactone drug-loaded electrospinning film with trabeculectomy in rabbits

Abstract

Background Scarring of filter bleb is a main cause of failure after trabeculectomy.Administration of anti-proliferation dugs during filtering surgery can maintain the opening of filtering pathway, but some serious complications occure after the drug use.Researches showed that polylactic acid caprolactone (PLCA) drug-loaded electrospinning film can release drug slowly, but its application in glaucoma is seldom. Objective The aim of this study was to evaluate the anti-scarring effects of non-penetrating trabeculectomy combined with sclera interlayer implantation of triamcinolone acetonide (TA)/PLCA drug-loaded electrospinning film in rabbit. Methods TA/PLCA drug-loaded electospinning film was prepared by electrospinning and its surface ultrastructure was observed under the scanning electron microscope.The drug release properties were detected by high performance liquid chromatograph.Ocular hypertensive models were established in New Zealand white rabbits by injecting carbomer into the anterior chamber of the right eyes, and the 40 models were randomized into 5 groups, 8 eyes for each group.TA/PLCA drug-loaded electrospun membrane, PLCA electrospun membrane or amniotic membrane was implanted beneath the scleral flap during trabeculectomy respectively in the TA/PLCA group, PLCA group or amniotic group, and 40 mg/ml TA was subconjunctivally injected in the TA group.Only trabeculectomy was performed in the simple trabeculectomy group.Intraocular pressure (IOP) was measured, and the shape of filtering bleb was examined under the slit lamp 1 week, 2, 4, 8 and 12 weeks after surgery.The section of filtering bleb was prepared 12 weeks after surgery for the histopathological examination.The use and management of experimental animals was in line with animal ethics. Results The similar three-dimensional reticular structure was seen between TA/PLCA and electrospun membrane with the fiber diameter 0.5-1.5 μm.TA was released stably for 14 days.All the filtering blebs were disappeared in the simple trabeculectomy group during 8-week duration after operation.At 12 weeks after operation, the functional bleb was found in all the 8 eyes of the TA/PLCA group, 5 eyes of PLCA group, 4 eyes of the amniotic group and 4 eyes of the TA group.The IOP was significantly different among the groups, with the lowest IOP in the TA/PLCA group and the highest IOP in the simple trabeculectomy group (all at P=0.000). Histopathological examination showed that the filtering pathway remained opening in all 8 eyes with the epithelization of bleb surface in the TA/PLCA group, and interspaces of the filtering pathway was explayed in the PLCA group, amniotic group and TA group, while fibrosis of filtering pathway was seen in the simple trabeculectomy group at 12 weeks after surgery. Conclusions TA/PLCA drug-loading electrospun membranes presents with nanoscale microstructure and good drug-release properties in vitro.Implantaion of TA/PLCA beneath the scleral flap during trabeculectomy can inhibit the fibrosis of filtering pathway. Key words: Glaucoma/therapy; Trabeculecutomy; Polylactic acid caprolactone/chemistry; Triamcinolone acetonide/pharmacology; Proliferation; Drug delivery systems; TA/PLCA drug-loaded electrospinning film; Rabbits