Influence of age, diabetes, and cataract on calcium, lipid-calcium, and protein-calcium relationships in human lenses.

PURPOSE Calcium is elevated in most cataractous human lenses and may contribute to cataractogenesis. In this study, age-related changes were examined in the total calcium content of clear human lenses and the binding of calcium to lens lipids and proteins. METHODS Total lens calcium was determined by atomic absorption spectroscopy. Calcium binding was measured by light scattering and measurement of calcium by atomic absorption spectroscopy in bound and unbound fractions. RESULTS The calcium content of clear human lenses decreased between 18 and 55 years of age and increased between 55 and 75 years, as well as in the presence of cataract. Total calcium levels in clear lenses from subjects with insulin-dependent diabetes did not differ from that in lenses of age-matched control subjects. In vitro binding studies have shown that lens lipids can bind nearly all the calcium present in the human lens. Age and cataract diminished the capacity of lens lipids to bind calcium. Calcium-induced light-scattering, measured in vitro for lens proteins, correlated with increasing age and cataract. CONCLUSIONS The data support the hypothesis that increased intracellular calcium concentrations and a diminished capacity of lens lipids to bind to calcium initiate a cascade of events that culminates in increased light-scattering from lipids and especially proteins. Calcium binding to lipid membranes cannot directly contribute to light-scattering in cataractous lenses. It has been suggested that most of the diffusible calcium in the lens is in the intercellular spaces and that lens lipids in the outer leaflet of the bilayer bind to that calcium. If so, this could account for the 150-fold difference between free and bound calcium levels in the lens.

[1]  G. Duncan,et al.  Distribution of non-diffusible calcium and sodium in normal and cataractous human lenses. , 1977, Experimental eye research.

[2]  A. Bron,et al.  Perinuclear lens retrodots: a role for ascorbate in cataractogenesis. , 1987, The British journal of ophthalmology.

[3]  A. Dawson,et al.  Calcium mobilisation modulates growth of lens cells. , 1996, Cell calcium.

[4]  A. Spector,et al.  The effect of calcium upon the reaggregation of bovine alpha crystallin. , 1973, Investigative ophthalmology.

[5]  C. Paterson,et al.  Ca(2+)-ATPase activity and lens lipid composition in reconstituted systems. , 1999, Experimental eye research.

[6]  R. Giordano,et al.  Inorganic element concentrations in cataractous human lenses. , 1992, Annals of ophthalmology.

[7]  M. Bally,et al.  Production of large unilamellar vesicles by a rapid extrusion procedure: characterization of size distribution, trapped volume and ability to maintain a membrane potential. , 1985, Biochimica et biophysica acta.

[8]  L. Takemoto,et al.  Evidence for reduced lipid order in plasma membranes from cataractous human lenses. , 1982, Current eye research.

[9]  R. Heyningen.  The human lens. II. Some observations on cataracts removed in Oxford, England. , 1972 .

[10]  S. Srivastava,et al.  Alterations in the light transmission through single lens fibers during calcium-mediated disintegrative globulization. , 1997, Investigative ophthalmology & visual science.

[11]  E. Disalvo,et al.  Optical properties of lipid dispersions induced by permeant molecules , 1991 .

[12]  P. Davies,et al.  Membrane permeability characteristics of perfused human senile cataractous lenses. , 1986, Experimental eye research.

[13]  G. Vrensen,et al.  Calcium localization and ultrastructure of clear and pCMPS-treated rat lenses. , 1995, Investigative ophthalmology & visual science.

[14]  C. Paterson,et al.  An analysis of 45Ca fluxes in the rabbit lens. , 1982, Current eye research.

[15]  J. VANMARLEa,et al.  Calcium and its Localization in Human Lens Fibres : An Electron Tomographic Study , 1997 .

[16]  R. Heyningen.  The human lens: III. Some observations on the post-mortem lens , 1972 .

[17]  F. Giblin,et al.  Calcium-induced high molecular weight proteins in the intact rabbit lens. , 1984, Experimental eye research.

[18]  C. Paterson,et al.  Calcium transport, Ca2(+)-ATPase, and lipid order in rabbit ocular lens membranes. , 1991, The American journal of physiology.

[19]  C. Paterson,et al.  Expression of sarco/endoplasmic reticular Ca(2+)-ATPase in human lens epithelial cells and cultured human lens epithelial B-3 cells. , 1999, Current eye research.

[20]  G. Duncan,et al.  Calcium, cell signalling and cataract , 1994, Progress in Retinal and Eye Research.

[21]  M. Bootman,et al.  Calcium regulation in tissue-cultured human and bovine lens epithelial cells. , 1993, Investigative ophthalmology & visual science.

[22]  K. Hightower.  The influence of calcium on protein synthesis in the rabbit lens. , 1983, Investigative ophthalmology & visual science.

[23]  K. Hightower,et al.  Cytotoxic effects of calcium on sodium-potassium transport in the mammalian lens. , 1982, Current eye research.

[24]  D. Borchman,et al.  Structural characterization of lipid membranes from clear and cataractous human lenses. , 1993, Experimental eye research.

[25]  D. Borchman,et al.  31P NMR quantification and monophasic solvent purification of human and bovine lens phospholipids , 2002, Lipids.

[26]  K. Hightower.  Cytotoxic effects of internal calcium on lens physiology: a review. , 1985, Current Eye Research.

[27]  W. Dean,et al.  Effect of oxidation on Ca2+ -ATPase activity and membrane lipids in lens epithelial microsomes. , 1999, Free radical biology & medicine.

[28]  I. Vorobyov,et al.  Conformational studies of sphingolipids by NMR spectroscopy. I. Dihydrosphingomyelin. , 2000, Biochimica et biophysica acta.

[29]  C. Paterson,et al.  ATPase activities of rabbit and bovine lens epithelial microsomes: a continuous fluorimetric assay study. , 1995, Current eye research.

[30]  H. Maisel,et al.  Evidence for a calcium activated protease specific for lens intermediate filaments. , 1984, Current eye research.

[31]  G. Benedek,et al.  Calcium-induced aggregation of bovine lens alpha crystallins. , 1972, Investigative ophthalmology.

[32]  C. Paterson,et al.  Plasma Membrane Calcium ATPase Gene Expression in Bovine Lens Epithelium , 2000, Ophthalmic Research.

[33]  C. Joo,et al.  Progressive opacification of hydrophilic acrylic intraocular lenses in diabetic patients. , 2002, Journal of cataract and refractive surgery.

[34]  D. Borchman,et al.  Ca2+-ATPase activity in the human lens. , 1989, Current eye research.

[35]  A. M. Leeuw,et al.  Calcium-binding lens membrane proteins , 1986, Documenta Ophthalmologica.

[36]  C. Paterson,et al.  The influence of calcium on the rabbit lens sodium pump. , 1993, Investigative ophthalmology & visual science.

[37]  D. Nicoli,et al.  On the calcium concentration of cataractous and normal human lenses and protein fractions of cataractous lenses. , 1976, Experimental eye research.

[38]  L. Bakas,et al.  Effect of encapsulated Ca2+ on the surface properties of curved phosphatidylcholine bilayers. , 1991, Biochimica et biophysica acta.

[39]  F. Bettelheim,et al.  Light scattering of normal human lens. III. Relationship between forward and back scatter of whole excised lenses. , 1985, Experimental eye research.

[40]  C. Paterson,et al.  Calcium ATPase activity and membrane structure in clear and cataractous human lenses. , 1997, Current eye research.

[41]  K. Bjerve,et al.  The calcium and magnesium content of the human lens and aqueous humour A study in patients with hypocalcemic and senile cataract , 1988, Acta ophthalmologica.

[42]  T. Murachi,et al.  Limited proteolysis of bovine lens alpha-crystallin by calpain, a Ca2+-dependent cysteine proteinase, isolated from the same tissue. , 1984, Biochimica et biophysica acta.

[43]  I. Vorobyov,et al.  Conformational studies of sphingolipids by NMR spectroscopy. II. Sphingomyelin. , 2000, Biochimica et biophysica acta.

[44]  C. Paterson,et al.  Ca2+-ATPase activity in the human lens. , 1989, Current Eye Research.

[45]  M. Narasu,et al.  Calcium ion binding to delta- and to beta-crystallins. The presence of the "EF-hand" motif in delta-crystallin that aids in calcium ion binding. , 1989, The Journal of biological chemistry.

[46]  K. Hightower,et al.  Regional distribution of calcium in alloxan diabetic rabbit lens. , 1989, Current Eye Research.

[47]  C. Paterson,et al.  Oxidative inhibition of Ca2+-ATPase in the rabbit lens. , 1989, Investigative ophthalmology & visual science.

[48]  N. Dilsiz,et al.  Determination of calcium, sodium, potassium and magnesium concentrations in human senile cataractous lenses , 2000, Cell biochemistry and function.

[49]  C. Paterson,et al.  Selective inhibition of membrane ATPases by hydrogen peroxide in the lens of the eye. , 1988, Basic life sciences.

[50]  C. Eckhert.  Elemental concentrations in ocular tissues of various species. , 1983, Experimental eye research.

[51]  D. Borchman,et al.  Interactions of Ca(2+) with sphingomyelin and dihydrosphingomyelin. , 2002, Biophysical journal.

[52]  D. Borchman,et al.  Role of cholesterol in the structural order of lens membrane lipids. , 1996, Experimental eye research.

[53]  G. Maraini,et al.  Cation pump activity and membrane permeability in human senile cataractous lenses. , 1982, Experimental eye research.

[54]  K. G. Brown,et al.  Atomic and Raman spectroscopy of the dipalmitoylphosphatidic acid-calcium complex and phase transitions. , 1986, Biochimica et biophysica acta.

[55]  V. Reddy,et al.  Calcium content and distribution in human cataract. , 1982, Experimental eye research.

[56]  J. Sredy,et al.  Phosphorylated intermediates of two Ca++-ATPases in membrane preparations from lens epithelial cells. , 1985, Current eye research.

[57]  J. Turnquist,et al.  Identification of the calmodulin-binding components in bovine lens plasma membranes. , 1985, European journal of biochemistry.

[58]  Y. Bardak,et al.  Lenticular Calcium, Magnesium, and Iron Levels in Diabetic Rats and Verapamil Effect , 1998, Ophthalmic Research.

[59]  P. D. Davies,et al.  Thapsigargin-coated intraocular lenses inhibit human lens cell growth , 1997, Nature Medicine.

[60]  S. Gandolfi,et al.  86-Rb efflux in normal and cataractous human lenses. , 1985, Current eye research.

[61]  S. Gandolfi,et al.  Human lens membrane cation permeability increases with age. , 1989, Investigative ophthalmology & visual science.

[62]  H. Cheng,et al.  The energy status of lenses from human donor eyes. , 1988, Experimental Eye Research.

[63]  L. Zimmerman,et al.  Calcium oxalate crystals within ocular tissues; a clinicopathologic and histochemical study. , 1958, A.M.A. archives of ophthalmology.

[64]  R. VAN HEYNINGEN,et al.  The human lens. 3. Some observations on the post-mortem lens. , 1972, Experimental eye research.

[65]  G. Duncan,et al.  Ion analyses of human cataractous lenses. , 1975, Experimental eye research.

[66]  G. Benedek,et al.  Cortical opacity, calcium concentration and fiber membrane structure in the calf lens. , 1980, Experimental eye research.

[67]  C. Paterson,et al.  Studies on the distribution of cholesterol, phospholipid, and protein in the human and bovine lens. , 1989, Lens and eye toxicity research.

[68]  D. Borchman,et al.  Conformational studies of sphingolipids by NMR spectroscopy , 2000 .

[69]  G. Duncan,et al.  Thapsigargin inhibits a potassium conductance and stimulates calcium influx in the intact rat lens , 1999, The Journal of physiology.

[70]  L. Bakas,et al.  Effect of the asymmetric Ca2+ distribution on the bilayer properties of phosphatidylcholine-sonicated vesicles. , 1989, Biochimica et biophysica acta.

[71]  D. Adams.  The rôle of calcium in senile cataract. , 1929, The Biochemical journal.

[72]  E. Disalvo,et al.  Thermodynamic factors determining the permeability barrier properties of lipid bilayers , 1985 .