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Thapsigargin-coated intraocular lenses inhibit human lens cell growth

Abstract

Cataract is responsible for rendering several million people blind throughout the world1 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 ceil growth within the capsular bag after surgery2. The resulting decline in visual acuity requires expensive laser treatment2, 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 system3, has confirmed that cells from a wide age range of donors proliferate in the absence of added serum protein4 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+)-ATPase5, greatly reduced cell growth in the capsular bag at relatively low coating concentrations (200 μM) but, more significantly, induced total cell death of the residual anterior epithelial cells at higher concentrations (>2 μM).

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Duncan, G., Wormstone, I., Liu, C. et al. Thapsigargin-coated intraocular lenses inhibit human lens cell growth. Nat Med 3, 1026–1028 (1997). https://doi.org/10.1038/nm0997-1026

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