Use of a polylysine–saporin conjugate to prevent posterior capsule opacification

Abstract

PURPOSE: To determine the feasibility of applying a polylysine-saporin (PLS) conjugate to the lens capsule at surgery to prevent lens epithelial cell (LEC) proliferation and posterior capsule opacification (PCO). SETTING: Department of Research & Development, Bausch & Lomb Surgical, and Department of Ophthalmology, Saint Louis University, St. Louis, Missouri, USA. METHODS: Fluorescein-labeled polylysine was applied to the lens capsule of rabbits after phacoemulsification and analyzed histologically to determine the extent of binding to the lens capsule and surrounding tissues. The cytotoxin saporin was conjugated to polylysine using bifunctional cross-linkers. This PLS conjugate was applied to LECs in culture and to the lens capsules of rabbits. These eyes were monitored for PCO. RESULTS: Polylysine primarily bound to the lens capsule membranes, with little or no binding to surrounding tissues. When PLS was added to LECs in culture, it was internalized and destroyed the cells. Of 9 rabbit eyes treated with PLS during surgery, 1 remained free of PCO for the life of the animal (40 weeks), while 6 showed a delay of cortical regrowth approximately 2 to 3 times that of control eyes. CONCLUSIONS: Polylysine bound selectively to the lens capsule membrane. The PLS conjugation resulted in a toxic agent that targeted the lens capsule and destroyed proliferating LECs. The application of a PLS conjugate during surgery may prevent PCO.