Abstract

Posterior capsular opacification (PCO) is caused by the proliferation and migration of residual lens epithelium cells (LECs) after extracapsular cataract extraction (ECCE). Rapamcin (RAPA) is known to be a potent immunosuppressive drug with anti-inflammatory and anti-proliferative effects. The aim of this study was to investigate the safety and efficacy of rapamycin sustained release from modified intraocular lens (IOLs) in the prevention of PCO in rabbits. Three types of IOLs were used, including the original IOL without modification, IOL with polylactide-glycoli acid (PLGA) coating (PLGA-IOL), and RAPA-loaded PLGA-IOL (RAPA-PLGA-IOL). Sixty New Zealand albino rabbits undergoing phacoemulsification in left eyes were randomly and equally divided into three groups. Group A was implanted with the original IOLs, group B was implanted with the PLGA-IOLs, and group C was implanted with the RAPA-PLGA-IOLs. All of the 60 treated left eyes were examined by a slit-lamp microscope. The concentrations of RAPA in the aqueous humor and blood were determined by high-performance liquid chromatography (HPLC), indicating an vivo release of drug from the polymer carrier. Anterior segment tissue was histologically examined, and wet posterior capsules were weighed. Six months after intervention the PCO was graded. The mean concentrations of RAPA in the aqueous humor from group C at 2 h, 1 days, 3 days, and 7 days after operation were 12.81 +/- 1.27 microg/ml, 14.57 +/- 0.99 microg/ml, 6.39 +/- 0.95 microg/ml, and 1.10 +/- 0.32 microg /ml respectively. The concentrations of RAPA in blood were undetectable. During the early days after the operation, the reactions of the anterior chamber from groups A and B were more severe than from group C. Our findings showed that the initial appearance of PCO in group C was much later than in the other two groups. The wet posterior capsules were weighed to be 0.3735 +/- 0.0943 g (group A), 0.3754 +/- 0.1093 g (group B), and 0.0432 +/- 0.0089 g (group C). Histological observation showed a similar phenomenon, that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups. Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.

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