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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References
Thylefors, B., Negrel, A.D., Pararajasegaram, R. & Dadzie, K.Y. Global data on blindness. Bull. World Health Org. 73, 115–121 (1995).
Apple, D.J. et al. Posterior capsule opacification. Surv. Ophthalmol. 37, 73–116 (1992).
Liu, C.S.C. et al. A study of human lens Cell growth in vitro: A model for posterior capsule opacification. Invest. Ophthalmol. Vis. Sci. 37, 906–914 (1996).
Wormstone, J.M. et al. Human lens Cell proliferation in a protein-free medium. Invest. Ophthalmol. Vis. Sci. 38, 396–404 (1997).
Thastrup, O., Cullen, P.J., Drobak, B.K., Hanley, M.R. & Dawson, A.P., Thapsigargin, a tumor promoter, discharges intraCellular Ca2+ stores by a specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc. Natl. Acad. Sci. USA. 87, 2544–2570 (1990).
Ishizaki, Y., Voyvodic, J.T., Burne, J.F. & Raff, M.C. Control of lens epithelial Cell survival. J. Cell Biol. 121, 899–908 (1993).
Raff, M.C., Barres, B.A., Burne, J.F., Coles, H.S. & Ishizaki, Y. Programmed Cell-death and the control of Cell survival-lessons from the nervous system. Science 262, 695–700 (1993).
Ibaraki, N., Ohara, K. & Miyamoto, T. Membranous outgrowth suggesting lens epithelial Cell proliferation in pseudophakic eyes. Am. J. Ophthalmol. 119, 706–711 (1995).
Cole, D.F. Comparative aspects of the intraocular fluids. in The Eye (eds. Davson, H. & Graham, LT.) 71–161 (Academic Press, London, 1974).
Powe, N.R. et al. Synthesis of the literature on visual-acuity and complications following cataract extraction with lens implantation. Arch. Ophthalmol. 112, 239–252 (1994).
Emery, J., Clark, D.S., Munsell, M. & Kelleher, P.J. Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial Cells: Eighteen month results of a phase I/II clinical study. Invest. Ophthalmol. Vis. Sci. 37, S758 (1996).
Behar-Cohen, F.F. et al. In vivo inhibition of lens regrowth by fibroblast growth factor 2-saporin. Invest. Ophthalmol. Vis. Sci. 36, 2434–2448 (1995).
Duncan, G. et al. Calcium mobilisation modulates growth of lens Cells. Cell Calcium 19, 83–89 (1996).
Ghosh, T.K., Bian, J., Short, A.D., Rybak, S.L. & Gill, D.I. Persistent intraCellular calcium pool depletion by thapsigargin and its influence on Cell growth. J. Biol. Chem. 266, 24690–24697 (1991).
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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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DOI: https://doi.org/10.1038/nm0997-1026
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