Abstract
Purpose: :
To determine if the perturbation of the actin cytoskeleton induced by latrunculin B (LAT-B) or H-7 facilitates clearance of residual lens epithelial cells (LECs) during lens surgery in live rabbits, and/or inhibits proliferation and migration of the residual LECs in cultured human lens capsules.
Methods: :
(1) 15 rabbits (30 eyes) underwent extracapsular lens extraction by phacoemulsification, in which 8 eyes were treated w/ LAT-B (5µM in the AC), 8 w/ DMSO (0.25%), 6 w/ H-7 (750µM), and 8 w/ H2O (2.5%). After the lens nucleus and major cortex had been removed from the capsular bag, the drug/vehicle was administered intracapsularly and maintained for 18-20 min, followed by a 2-min intracapsular irrigation/aspiration w/ plain BSS (H-7/H2O protocol) or BSS containing the corresponding drug/vehicle (LAT-B/DMSO protocol). After surgery the rabbits were sacrificed and the lens capsules were prepared, fixed and photographed. The remaining LECs on the capsule were evaluated by cell area measurements. (2) Following sham cataract surgeries w/ donated human eyes, 14 lens capsules were prepared and cultured by the standard technique; 3 were treated w/ H-7 (300µM), 4 w/ BSS, 3 w/ LAT-B (2µM), and 4 w/ DMSO (0.25%). The capsule cultures lasted 4 weeks and PCO formation was photographed and scored by a 4-point scale at least once weekly.
Results: :
In live rabbits, LAT-B significantly removed ~15% additional LECs from the capsule, compared to any other treatment. H-7 had no effect on the clearance of LECs. In cultured human capsules, all 3 capsules receiving H-7 showed no capsule wrinkling or PCO, while the capsules receiving BSS, DMSO or LAT-B showed apparent capsule wrinkling and diffuse and thick PCO.
Conclusions: :
The rabbit experiment suggests that treatment w/ LAT-B during surgery seems to facilitate the clearance of LECs, which may reduce the possibility of PCO after surgery. The human lens culture shows that H-7 prevents PCO probably by inhibiting proliferation and migration of LECs and capsule contractility. This study indicates that pharmacological perturbation of the actin cytoskeleton may inhibit PCO.
Keywords: posterior capsular opacification (PCO) • cytoskeleton • drug toxicity/drug effects