title: 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, of which 13 were treated with H-7 (50, 100 or 300 μM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10 μM), 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 one 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 2-3 weeks. 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 300 μM H-7 (n = 8, p < 0.001) or 10 μM LAT-B culture (n = 3, p = 0.002).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Aravind Medical Research Foundation, Dr. G. Venkataswamy Eye Research Institute, No.1, Anna Nagar, Madurai, 625020, Tamil Nadu, India.
authors.forename: Jeyalakshmi
authors.initials: J
authors.lastname: Sureshkumar
authors.forename: Aravind
authors.initials: A
authors.lastname: Haripriya
authors.forename: Veerappan
authors.initials: V
authors.lastname: Muthukkaruppan
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaufman
authors.forename: Baohe
authors.initials: B
authors.lastname: Tian
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D058442:Capsule Opacification / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D009924:Organ Culture Techniques; D057852:Posterior Capsule of the Lens / Q000187:drug effects*; D053778:Thiazolidines / Q000494:pharmacology*; D014019:Tissue Donors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D053778:Thiazolidines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C037068:latrunculin B