Thapsigargin-coated intraocular lenses inhibit human lens cell growth.
Cataract is responsible for rendering several million people blind throughout the world and is also by far the most common cause of low visual acuity. Although cataract surgery is common, routine and effective, posterior capsule opacification (PCO) occurs in 30-50% of patients following modern cataract surgery. This condition arises from stimulated cell growth within the capsular bag after surgery. The resulting decline in visual acuity requires expensive laser treatment, and PCO therefore prevents modern cataract surgery from being carried out routinely in underdeveloped countries. The present study, using a human lens capsular bag culture system, has confirmed that cells from a wide age range of donors proliferate in the absence of added serum protein and explains why PCO is such a common problem even in aged patients. This study also provides one possible solution for PCO by using polymethylmethacrylate (PMMA) implanted intraocular lenses as a drug delivery system. PMMA lenses coated with thapsigargin, a hydrophobic inhibitor of endoplasmic reticulum (ER) (Ca2+)-ATPase, greatly reduced cell growth in the capsular bag at relatively low coating concentrations (200 nM) but, more significantly, induced total cell death of the residual anterior epithelial cells at higher concentrations (>2 microM).
Duncan
G
G
School of Biological Sciences, University of East Anglia, Norwich, UK. g.duncan@uea.ac.uk
Wormstone
I M
IM
Liu
C S
CS
Marcantonio
J M
JM
Davies
P D
PD
D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002386:Cataract / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007903:Lens Capsule, Crystalline / Q000166:cytology* / Q000187:drug effects*; D007910:Lenses, Intraocular / Q000009:adverse effects; D008768:Methylmethacrylates; D008954:Models, Biological; D019284:Thapsigargin / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D008768:Methylmethacrylates; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases