Comparison of posterior capsule opacification in rabbit eyes receiving different administrations of rapamycin

Graefes Arch Clin Exp Ophthalmol. 2014 Jul;252(7):1111-8. doi: 10.1007/s00417-014-2656-9. Epub 2014 Jun 1.

Abstract

Background: Posterior capsule opacification (PCO) is a common complication after cataract surgery. The purpose of this study was to determine the effects of three administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for 12 weeks.

Methods: Eighty rabbits were divided into four groups, according to the different administrations of RAPA which they received. These were: (1) the control group, (2) the irrigation-treated group - 5 ng/ml intraoperative RAPA irrigation solution, (3) the eye-drop-treated group - 2 mg/ml RAPA eye drops, and (4) the IOL-treated group - RAPA-poly(lactic-co-glycolic) acid (PLGA) loaded on the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs). All right eyes were treated with lens extraction plus IOL implantation, receiving relative administrations of RAPA. RAPA concentrations in the aqueous humour were determined by high performance of liquid chromatography (HPLC). The anterior chamber (AC) response was observed through slit-lamp biomicroscopy. After 12 weeks, the degree of PCO was determined by clinical evaluation. The histological sections, immunohistochemistry expression of proliferating cell nuclear antigen (PCNA) in the lens capsule were conducted.

Results: In the early period, AC response for both experimental and control eyes were similar. In the IOL-treated group, RAPA reached its peak at 25.68 ± 0.74 μg/ml on the 4th day, and it was detectable until 8 weeks afterwards. However, in the other groups, RAPA could not be detected all the time. Compared with other groups, in the IOL-treated group, PCO was greatly alleviated; only a few layers of the lens epithelial cells (LECs) and a little proliferative material around the posterior capsules, and a significantly weak expression of PCNA in the nuclei of LECs. By contrast, there was no significant statistical difference in eye-drop-treated or irrigation-treated eyes and control eyes respectively.

Conclusions: Intraocular RAPA-PLGA-IOL was a promising, effective, and safe administration to prevent PCO compared with other methods in the rabbit PCO model.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aqueous Humor / metabolism
  • Biomarkers / metabolism
  • Capsule Opacification / metabolism
  • Capsule Opacification / pathology
  • Capsule Opacification / prevention & control*
  • Immunoenzyme Techniques
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacokinetics
  • Lens Implantation, Intraocular
  • Ophthalmic Solutions
  • Phacoemulsification
  • Posterior Capsule of the Lens / drug effects*
  • Posterior Capsule of the Lens / metabolism
  • Posterior Capsule of the Lens / pathology
  • Postoperative Complications / metabolism
  • Postoperative Complications / pathology
  • Postoperative Complications / prevention & control*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rabbits
  • Sirolimus / administration & dosage*
  • Sirolimus / pharmacokinetics

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Ophthalmic Solutions
  • Proliferating Cell Nuclear Antigen
  • Sirolimus