Abstract
The lens possesses an impressive array of G-protein receptors that are coupled to the release of intracellular calcium. They include members of the muscarinic, adrenergic and purinergic families and activation of the former has been implicated in cataract for some time. There are several possible mechanisms whereby activation of such receptors could give rise to cataract. A prolonged increase in intracellular calcium would be expected to activate proteases such as calpain and so could induce unscheduled and irreversible breakdown of important structural proteins. It has recently been shown that activation of G-protein receptors also modulates lens cell growth, and any interference with the highly controlled pattern of cell growth and development within the lens is also likely to have catastrophic consequences. If the calcium store is totally inactivated in lens cells, for example by exposure to thapsigargin, then growth ceases. This finding provides a means of inhibiting the lens cell growth which leads to posterior capsular opacification (PCO). For example, it has been shown that thapsigargin-coated intraocular lenses totally inhibit lens cell growth within cultured capsular bags, and if this technology could be transferred to the clinic then it could provide a simple and relatively inexpensive means of preventing PCO.
Similar content being viewed by others
Article PDF
References
Duncan G, Bushell AR . Ion analyses of human cataractous lenses. Exp Eye Res 1975;20:223–30.
Marcantonio JM, et al. Classification of human senile cataracts by nuclear colour and sodium content. Exp Eye Res 1980;31:227–37.
Hodge WG, Whitcher JP, Satariano W . Risk factors for age-related cataracts. Epidemiol Rev 1995;17:336–46.
Leopold IH, Barnert AH . Steroids in ophthalmology. Adv Ophthalmol 1967;18:1–64.
Augusteyn RC . Protein modification in cataract: possible oxidative mechanisms. In: Duncan G, editor. Mechanisms of cataract formation in the human lens. New York: Academic Press, 1981:72–115.
Evans JR, et al. Age-related nuclear lens opacities are associated with reduced growth before one year of age. Invest Ophthalmol Vis Sci 1998;39:1740–4.
Jacques PF, et al. Long term vitamin C supplement use and prevalence of early age-related lens opacities. Am J Clin Nutr 1997;66:911–6.
Leske MC, et al. Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract. Ophthalmology 1998;105:831–6.
Spector A, Garner WH . Hydrogen peroxide and human cataract. Exp Eye Res 1981;33:673–81.
Azuma M, et al. Activation of calpain in lens: a review and proposed mechanism. Exp Eye Res 1997;64:529–38.
Duncan G, Jacob TJC . Calcium and the physiology of cataract. Ciba Found Symp 1984;106:132–48.
Sanderson J, Duncan G . pCMPS-induced changes in lens membrane permeability and transparency. Invest Ophthalmol Vis Sci 1993;34:2518–25.
Delamere NA, Paterson CA . Hypocalcaemic cataract. In: Duncan G, editor. Mechanisms of cataract formation in the human lens. New York: Academic Press, 1981:60–72.
Duncan G, et al. Human lens membrane permeability increases with age. Invest Ophthalmol Vis Sci 1989;30:1855–9.
Marcantonio JM, Duncan G, Rink H . Calcium-induced opacification and loss of protein in the organ-cultured bovine lens. Exp Eye Res 1986;42:617–30.
Hightower KR, Riley MV, McCready J . Regional distribution of calcium in alloxan diabetic lens. Curr Eye Res 1989;8:517–21.
Duncan G, Williams MR, Riach RA . Calcium, cell signalling and cataract. Prog Ret Eye Res 1994;13:623–52.
Vivekanandan S, Lou MF . Evidence for the presence of phosphoinositide cycle and its involvement in signal transduction in the rabbit lens. Curr Eye Res 1989;8:101–12.
Knorr M . Modulation of cytosolic free calcium concentrations by PDGF isoforms in cultured bovine lens epithelial cells. Exp Eye Res 1992;55:S623.
McAvoy JW, Chamberlain CG . Growth factors in the eye. Prog Growth Factor Res 1990;2:29–31.
Reid TW . Growth control of cornea and lens epithelial cells. Prog Ret Eye Res 1994;13:507–54.
Williams MR, et al. Acetylcholine receptors are coupled to mobilisation of intracellular calcium in cultured human lens cells. Exp Eye Res 1993;57:381–4.
Thomas GR, Duncan G, Sanderson J . Acetylcholine-induced membrane potential oscillations in the intact lens. Invest Ophthalmol Vis Sci 1998;39:111–9.
Thomas GR, et al. The human lens possesses actylcholine receptors that are functional throughout life. Exp Eye Res 1997;64:849–52.
Duncan G, et al. Calcium mobilisation modulates growth of lens cells. Cell Calcium 1996;19:83–9.
Shaffer RN, Hethrington J . Anticholinesterase drugs and cataract. Am J Ophthalmol 1966;64:613–8.
Fraser PJ, Duncan G, Tomlinson J . Effects of a cholinesterase inhibitor on salmon lens: a possible cause for the increased incidence of cataract in salmon Salmo solar. Exp Eye Res 1989;49:293–8.
Kaufman PL, Axelsson U, Barany EH . Atropine inhibition of ecothiophate cataractogenesis in monkeys. Arch Ophthalmol 1977;95:1262–8.
Thomas GR, et al. The human lens possesses acetylcholine receptors that are functional throughout life. Exp Eye Res 1997;67:849–52.
Honkanen RE, Howard EF, Abdel-Latif AA . M3 muscarinic receptor subtype predominates in the bovine iris sphincter smooth muscle and ciliary processes. Invest Ophthalmol Vis Sci 1990;31:590–3.
Marcantonio JM, Vrensen GFJM . Cell biology of posterior capsular opacification. Eye 1999;13:482–6.
Duncan G, et al. Thapsigargin-coated intraocular lenses inhibit human lens cell growth. Nature Med 1997;3:1026.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Duncan, G., Wormstone, I. Calcium cell signalling and cataract: Role of the endoplasmic reticulum. Eye 13, 480–483 (1999). https://doi.org/10.1038/eye.1999.125
Issue Date:
DOI: https://doi.org/10.1038/eye.1999.125
Keywords
This article is cited by
-
Quantitative X-ray tomographic analysis reveals calcium precipitation in cataractogenesis
Scientific Reports (2021)
-
Connexin43 and connexin50 channels exhibit different permeability to the second messenger inositol triphosphate
Scientific Reports (2020)
-
A mutation in the start codon of γ-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain
Mammalian Genome (2013)
-
Spermidine Delays Eye Lens Opacification in vitro by Suppressing Transglutaminase-Catalyzed Crystallin Cross-Linking
The Protein Journal (2011)
-
Defensive Role of Quercetin Against Imbalances of Calcium, Sodium, and Potassium in Galactosemic Cataract
Biological Trace Element Research (2007)