Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro

Abstract

Background To determine whether the cytoskeletal drugs H-7 and Latrunculin B (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens capsular bag. Methods Following extracapsular cataract (lens) extraction in human donor eyes, the capsular bag was prepared and cultured by standard techniques. Forty-eight capsular bags were studied, in which 13 were treated with H-7 (50, 100 or 300μM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10μM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular bags were from paired eyes of 20 donors with 1 bag being treated with H-7/LAT-B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal drug/vehicle was replaced every 3–4 days for 4 weeks. PCO was assessed daily using inverted phase-contrast microscopy and scored on a 4-point scale. Results In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the anterior capsule migrated to and proliferated on the posterior capsule by 3–7 days and apparent LEC growth on the posterior capsule with severe capsular wrinkling (PCO Grade 3) was seen by 2-3weeks. When treated continuously with H-7 or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were inhibited in a dose-dependent manner, with the inhibition being complete (PCO Grade 0) in the 300μM H-7 (n=8, p<0.001) or 10μM LAT-B culture (n=3, p=0.002). Conclusion H-7 and LAT-B dose-dependently inhibited PCO formation in the cultured human lens capsular bags, suggesting that cytoskeletal drugs might prevent PCO formation after surgery in the human eye.

Tropomyosin 3.1 Association With Actin Stress Fibers is Required for Lens Epithelial to Mesenchymal Transition

“…49 As expected capsular wrinkling can be inhibited by treatment with the actin depolymerizing agent, latrunculin B. 50 Although latrunculin B can inhibit capsular wrinkling, it is a potent G-actin sequestering agent, and nondiscriminately disassembles dynamic F-actin networks. By targeting Tpm3.1, the F-actin stress fibers at the basal regions of epithelial cells adjacent to the lens capsule can be selectively targeted, possibly leading to reduced capsular wrinkling.…”

Histone Deacetylase Inhibitors Trichostatin A and Vorinostat Inhibit TGFβ2-Induced Lens Epithelial-to-Mesenchymal Cell Transition

“…include 5-fluorouracil, methotrexate, colchicine, mitomycin, 31,44 protease inhibitors, 13,27,45 cytoskeletal drugs, 46 aldose reductase inhibitors, 43 chelators, 47 small interfering RNAs, 48 and signal transduction inhibitors. 49 Gene transfer techniques also have been investigated.…”

The Development, Growth, and Regeneration of the Crystalline Lens: A Review

“…128 It has also been observed that PCO can be inhibited in vitro by using pharmaceutical agents targeting the cytoskeleton. 129 The cytoskeleton is typically involved in transducing external mechanical cues. Thus, inhibiting this mechanosensation in LECs may disrupt cytoskeleton-based signalling activity and potentially decouple the cellular response from mechanotransductive signals.…”