Abstract
An adult lens contains two easily discernible, morphologically distinct compartments, the epithelium and the fiber-cell mass. The fiber-cell mass provides the lens with its functional phenotype, transparency. Metabolically, in comparison to the fiber cells the epithelium is the more active compartment of the ocular lens. For the purposes of this review we will only discuss the surface epithelium that covers the anterior face of the adult ocular lens. This single layer of cells, in addition to acting as a metabolic engine that sustains the physiological health of this tissue, also works as a source of stem cells, providing precursor cells, which through molecular and morphological differentiation give rise to fiber cells. Morphological simplicity, defined developmental history and easy access to the experimenter make this epithelium a choice starting material for investigations that seek to address universal questions of cell growth, development, epithelial function, cancer and aging. There are two important aspects of the lens epithelium that make it highly relevant to the modern biologist. Firstly, there are no known clinically recognizable cancers of the ocular lens. Considering that most of the known malignancies are epithelial in origin this observation is more than an academic curiosity. The lack of vasculature in the lens may explain the absence of tumors in this tissue, but this provides only a teleological basis to a very important question for which the answers must reside in the molecular make-up and physiology of the lens epithelial cells. Secondly, lens epithelium as a morphological entity in the human lens is first recognizable in the 5th–6th week of gestation. It stays in this morphological state as the anterior epithelium of the lens for the rest of the life, making it an attractive paradigm for the study of the effects of aging on epithelial function. What follows is a brief overview of the present status and lacunae in our understanding of the biology of the lens epithelium.
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REFERENCES
Albert, D. M., Rabson, A. S., Grimes, P. A., and von Sallmann, L. (1969) Neoplastic transformation in vitro of hamster lens epithelium by Simian Virus 40, Science 164: 1077–1078.
Andersson, M., Sjostrand, J., and Karlsson, J. (1998) Proteolytic cleavage of N-Succ-Leu-Leu-Val-Tyr-AMC by the proteosome in lens epithelium from clear and cataractous human lens. Exp. Eye Res. 67: 231–236.
Andley, U. P., Rhim, J. S., Chylack, L. T., and Fleming, T. P. (1994) Propagation and immortalization of human lens epithelial cells in culture. Invest. Ophthalmol. and Vis. Sci. 35: 3094–3102.
Andley, U. P., Song, Z., Wawrousek, E. F., and Bassnett, S. (1998) The molecular chaperone ?A-crystallin enhances lens epithelial cell growth and resistance to UVA stress. J. Biol. Chem. 273: 31252–31261.
Appleby, D. W. and Modak, S. P. (1977) DNA degradation in terminally differentiating lens fiber cells from chick embryos. Proc. Natl. Acad. Sci. U.S.A. 74: 5579–5583.
Arita, T., Lin, L. R., Susan, S. R., and Reddy, V. N. (1990) Enhancement of differentiation of human lens epithelium in tissue culture by changes in cell-substrate adhesion. Invest. Ophthalmol. and Vis. Sci. 31: 2395–2404.
Arita, T., Murata, Y., Lin, L. R., Tsuji, T., and Reddy, V. N. (1993) Synthesis of lens capsule in longterm culture of human lens epithelial cells. Invest. Ophthalmol. and Vis. Sci. 34: 355–362.
Balaram, M., Tung, W. H., Kuszak, J. R., Ayaki, M., Shinohara, T., and Chylack, Jr., L. T. (2000) Noncontact specular microscopy of human lens epithelium. Invest. Ophthalmol. and Vis. Sci. 41: 474–481.
Bassnett, S., Kuszak, J. R., Reinisch, L., Brown, H. G., and Beebe, D. C. (1994) Intercellular communication between epithelial and fiber cells of the eye lens. J. Cell Sci. 107: 799–811.
Beebe, D. and Piatigorsky, J. (1977) The control of ?-crystallin gene expression during lens cell development: dissociation of cell elongation, cell division, ?-crystallin synthesis and ?-crystallin mRNA accumulation. Dev. Biol. 59: 174–182.
Becker, B. and Cotlier, E. (1962) Distribution of rubidium-86 accumulated in the rabbit lens. Invest. Ophthalmol. and Vis. Sci. 1: 642–645.
Bergner, A. and Glaesser, D. (1979) Demonstration of a magnesium-and calcium-dependent ATPase on the outer surface of bovine lens epithelial cells. Ophthalmic Res. 11: 322–323.
Bloemendal, H. et al. (1980) SV40-transformed hamster lens epithelial cells: A novel system for the isolation of cytoskeletal messenger RNAs and their translation products. Exp. Eye Res. 31: 513–525.
Bloemendal, H., Enzlin, J. H., Van Rijk, A. A., and Jansen, H. J. (1997) Biochemical differences between three subcell-lines derived from SV40-transformed hamster lens cells. Exp. Eye Res. 64: 1037–1041.
Bloemendal, H. (1991) Disorganization of membranes and abnormal intermediate filament assembly lead to cataract. Invest. Ophthalmol. and Vis. Sci. 32: 445–455.
Bodnar, A. G. et al. (1998) Extensions of life span by introduction of telomerase into normal human cells. Science 279: 349–352.
Brochman, D., Delamere, N. A., and Paterson, C. A. (1989) Ca2C-ATPase activity in the human lens. Curr. Eye Res. 8: 1049–1054.
Brenner, W. and Grabner, G. (1982) Unscheduled DNA repair in human lens epithelium following in vivo and in vitro UV irradiation. Ophthalmic Res. 14: 160–167.
Brown, H. G., Passas, G. D., Ireland, M. E., and Kuszak, J. R. (1990) Ultrastructural, biochemical and immunologic evidence of receptor-mediated endocytosis in the crystalline lens. Invest. Ophthalmol. and Vis. Sci. 31: 2579–2592.
Brown, N. A. P. and Bron, A. J. (1987) An estimate of the human cell size in vivo. Exp. Eye Res. 44: 899–906.
Campisi, J. (1999) Replicative senescence and immortalization. In: The Molecular Basis of Cell Cycle and Growth Control ( Stein, G. S., Baserga, R., Giordano, A., and Denhardt, D. T., eds.), New York, Wiley-Liss, Inc, pp. 348–373.
Chandy, K. G. and Gutman, G. A. (1995) Voltage-gated potassium channel genes. In: Ligand and Voltage-gated Ion Channels ( Norh, N. A., ed.), CRC, Boca Raton, FL, pp. 1–71.
Cheng, Q., Lichtstein, D., Russel, P., and Zigle, S. (2000) Use of lipophilic cation to monitor electrical membrane potential in the intact rat lens. Invest. Ophthalmol. and Vis. Sci. 41: 482–487.
Chylack, L. T. (1971) Control of glycolysis in the lens. Exp. Eye Res. 11: 280–293.
Colitz, C. M. H., Davidson, M. G., and McGahan, M. C. (1999) Telomerase activity in lens epithelial cells of normal and cataractous lenses. Exp. Eye Res. 69: 641–649.
Colitz, C. M., Malarkey, D., Dykstra, M. J., McGahan, M. C., and Davidson, M. G. (2000) Histologic and immunohistochemical characterization of lens capsular plaques in dogs with cataracts. Am. J. Vet. Res. 61: 139–143.
Collison, D. J., Coleman, R. A., James, R. S., Carey, J., and Duncan, G. (2000) Characterization of Muscarinic receptors in human lens cells by pharmacologic and molecular techniques. Invest. Ophthalmol. and Vis. Sci. 41: 2633–2641.
Coulombre, J. L. and Coulombre, A. J. (1963) Lens development: fiber elongation and lens orientation. Science 142: 1489–1490.
Courtois, Y., Simonneau, L., Tassin, J., Laurent, M. V., and Malaise, E. (1978) Spontaneous transformation of bovine lens epithelial cells. Differentiation 10: 23–30.
Davidson, M. G., Harned, J., Grimes, A. M., Duncan, G., Wirmstone, I. M., and McGahan, M. C. (1998) Transferrin in after-cataract and as a survival factor for lens epithelium. Exp. Eye Res. 66: 207–215.
Dahm, R., Marle, J. V., Prescott, A. R., and Quinlan, R. A. (1999) Gap junctions containing ?8-connexin (MP70) in the adult mammalian lens epithelium suggests a reevaluation of its role in the lens. Exp. Eye Res. 69: 45–56.
Dillon, J. (1991) The photophysics and photobiology of the eye. J. Photophys. Photobiol. 10: 23–40.
Duncan, G. and Jacob, T. J. C. (1984) Influence of external calcium and glucose on internal total and ionized calcium in rat lens. J. Physiol. 357: 485–493.
Egan, C. A., Savre-Train, I., Shay, J. W., Wilson, S. E., and Bourne, W. M. (1998) Analysis of telomere lengths in human corneal endothelial cells from donors of different ages. Invest. Ophthalmol. and Vis. Sci. 39: 648–653.
Eguchi, G. and Kodama, R. (1979) A study of human senile cataract: growth and differentiation of lens epithelial cell in in vitro cell culture. Ophthalmic Res. 11: 308–315.
Fagerholm, P. P. and Philpsin, B. T. (1981) Human lens epithelium in normal and cataractous lenses. Invest. Ophthalmol. and Vis. Sci. 21: 408–414.
Ferber, D. (1999) Immortalized cells seem cancer-free so far. Science 283: 154–155.
Fischbarg, J. et al. (1999) Transport of fluid by lens epithelium. Am. J. Physiol. 276: C548–557.
Francois, J. and Rabaey, M. (1951) Examination of the lens by phase-contrast microscopy. Br. J. Ophthalmol. 35: 352–355.
Fridovich, I. (1986) Biological effects of superoxide radical. Arch. Biochem. Biophys. 247: 1–11.
Garcia-Porrero, J. A., Colvee, E., and Ojeda, J. L. (1984) The mechanism of cell death and phagocytosis in the early chick lens morphogenesis: a scanning electron microscopy and cytochemical approach. Anat. Rec. 208: 123–136.
Garner, W., Garner, M., and Spector, A. (1983) H?O?-induced uncoupling of bovine lens Na_K ATPase. Proc. Natl. Acad. Sci. U.S.A. 80: 2044–2048.
Garner, M. and Horwitz, J. (1994) Catalytic subunit isoforms of mammalian lens Na_K ATPase. Curr. Eye Res. 13: 65–77.
Giblin, F. (2000) Glutathione. A vital lens antioxidant. J. Ocular Pharmacol. Therapeutics 16: 121–135.
Giblin, F., McReady, J., Schrimscher, L., and Reddy, V. (1987) Peroxide-induced effects on lens cation transport following inhibition of glutathione reductase activity in vitro. Exp. Eye Res. 45: 77–91.
Giblin, F. J., Nies, D. E., and Reddy, V. N. (1981) Stimulation of the hexose monophosphate shunt in rabbit lens in response to oxidation of glutathione. Exp. Eye Res. 33: 289–298.
Giles, K. M. and Harris, J. E. (1959) The accumulation of 14C from uniformly labeled glucose by the normal and diabetic rabbit lens. Am. J. Ophthalmol. 48: 508–551.
Glaesser, D., Rattke, W., and Iwig, M. (1979) Bovine lens epithelium: A suitable model for studying growth control mechanisms. C6-substituted purines inhibit cell flattening and growth stimulation of G0 cells. Exp. Cell Res. 122: 281–292.
Glucksmann, A. (1951) Cell death in normal vertebrate ontogeny. Biol. Rev. 26: 59–86.
Goodenough, D. A., Dick, J. S. B., and Lyons, J. E. (1980) Lens metabolic cooperation: a study of mouse lens transport and permeability visualized with freeze-substitution autoradiography and electron microscopy. J. Cell Biol. 86: 576–689.
Goodenough, D. A., Goliger, J. A., and Paul, D. L. (1996) Connexins, connexons and intercellular communication. Ann. Revs. Biochem. 65: 475–502.
Goodenough, D. A. (1992) The crystalline lens. A system networked by gap junctional intercellular communication. Semin. Cell Biol. 3: 49–58.
Gorin, M. B., Yancey, S. B., Cline, J., Revel, J.-P., and Horwitz, J. (1984) The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning. Cell 39: 49–59.
Gyorothy, W. C., Snavely, M. R., and Gerrong, N. D. (1971) Some aspects of transport and digestion in the lens of the normal young adult rat. Exp. Eye Res. 12: 112–119.
Grainger, R. M. (1992) Embryonic lens induction: shedding light on vertebrate tissue determination. Trends Genet. 8: 349–355.
Grant, M. E., Kefalides, N. A., and Prockop, D. J. (1972) The biosynthesis of basement membrane collagen in embryonic chick lens. 1. Delay between the synthesis of polypeptide chains and the secretion of collagen by matrix-free cells. J. Biol. Chem. 247: 3539–3544.
Guggenmoos-Holtzmann, I., Engel, B., Henke, V., and Naumann, G. O. H. (1989) Cell density of human lens epithelium in women higher than in men. Invest. Ophthalmol. and Vis. Sci. 30: 330–332.
Hales, A. M., Schultz, M. W., Chamberlain, C. G., and McAvoy, J. W. (1994) TGF-?1 induces lenscells to accumulate a smooth muscle actin, a marker for subcapsular cataracts. Curr. Eye Res. 13: 885–890.
Hales, A. M., Chamberlain, C. G., Dreber, B., and McAvoy, J. W. (1990) Intravitreal injection of TGF-b induces cataracts in rats. Invest. Ophthalmol. and Vis. Sci. 40: 3231–3236.
Hamada, Y. and Okada, T. S. (1978) In vitro differentiation of cells of the lens epithelium of human fetus. Exp. Eye Res. 26: 91–97.
Hamada, Y., Watanabe, K., Aoyama, H., and Okada, T. S. (1979) Differentiation and dedifferentiation of rat lens epithelial cells in short-and long-term cultures. Dev. Growth Differ. 21: 205–220.
Hamann, S. et al. (1998) Aquaporins in complex tissues: distribution of aquaporins 1–5 in human and rat eye. Am. J. Physiol. 274: C1332-1345.
Harding, C. V., Reddan, J. R., Unakar, N. J., and Bagchi, M. (1971) The control of cell division in the ocular lens. Int. Rev. Cytol. 31: 215–230.
Harding, J. J. and Crabbe, J. C. (1984) The lens: development, proteins, metabolism and cataract. In: The Eye ( Davson, H., ed.), New York, Academic Press, pp. 207–492.
Harocopos, G. J., Alvares, K. M., Kolker, A. E., and Beebe, D. C. (1998) Human age-related cataract and lens epithelial cell death. Invest. Ophthalmol. and Vis. Sci. 39: 2696–2706.
Harris, J. E. and Becker, B. (1965) Cation transport of the lens. Invest. Ophthalmol. and Vis. Sci. 4: 709–722.
Hay, E. D. and Zuk, A. (1995) Transformations between epithelium and mesenchyme: Normal, pathological and experimentally induced. Am. J. Kidney Disease 26: 678–690.
Hightower, K. R. and McReady, J. P. (1991) Effect of selenite on epithelium of cultured rabbit lens. Invest. Ophthalmol. and Vis. Sci. 32: 406–409.
Hightower, K. R., Reddan, J. R., McReady, J. P., and Dziedzic, D. C. (1994) Lens epithelium: a primary target of UVG irradiation. Exp. Eye Res. 59: 557–564.
Hightower, K. R. (1995) The role of the lens epithelium in development of UV cataract. Curr. Eye Res. 14: 71–78.
Huang, L. L., Shang, F., Novell Jr., T. R., and Taylor, A. (1995) Degradation of differential oxidized alpha-crystallins in bovine lens epithelial cells. Exp. Eye Res. 61: 45–54.
Huxtable, R. J. (1992) Physiological actions of taurine. Physiol. Rev. 72: 101–163.
Ibaraki, N., Chen, S. C., Lin, L. R., Okamoto, H., Pipas, J. M., and Reddy, V. N. (1998) Human lens epithelial cell line. Exp. Eye Res. 67: 577–585.
Ibaraki, N., Lin, L. R., and Reddy, V. N. (1996) A study of growth factor receptors in human lens epithelial cells and their relationship to fiber differentiation. Exp. Eye Res. 63: 683–692.
Inoue, K., Kubota, S., Tsuru, T., Araie, M., and Seyama, Y. (2000) Cholesterol induces apoptosis of corneal endothelial and lens epithelial cells. Invest. Ophthalmol. and Vis. Sci. 41: 991–997.
Ireland, M., Lieska, N., and Maisel, H. (1983) Lens actin: purification and localization. Exp. Eye Res. 37: 393–408.
Ishizaki, Y., Jacobson, M. D., and Raff, M. (1998) A role for caspases in lens filter differentiation. J. Cell Biol. 140: 153–158.
Ishizaki, Y., Voyvodic, J. T., Burne, J. F., and Raff, M. C. (1993) Control of lens epithelial cell survival. J. Cell Biol. 121: 899–908.
Jacob, T. J. C. (1983) A direct measurement of intracellular free calcium within the lens. Exp. Eye Res. 36: 451–453.
Jacob, T. J. C. (1987) Human lens epithelial cells in culture: A quantitative evaluation of growth rate and proliferative capacity. Exp. Eye Res. 45: 93–104.
Jacob, A. G. and Sater, A. K. (1988) Features of embryonic induction. Development 104: 341–359.
Jean, D., Ewan, K., and Gruss, P. (1998) Molecular regulators involved in vertebrate eye development. Mechanisms of Deûelopment 76: 3–18.
Kannan, R., Yi, J. R., Zlokovic, B. V., and Kaplowitz, N. (1995) Molecular characterization of a reduced glutathione transporter in the lens. Invest. Ophthalmol. and Vis. Sci. 36: 1785–1792.
Kantrow, M. et al. (1998) Differential display detects altered gene expression between cataractous and normal human lenses. Invest. Ophthalmol. and Vis. Sci. 39: 2344–2354.
Karim, A. J. A., Jacob, T. J., and Thompson, G. M. (1987) Cell density, morphology and mitotic index in normal and cataractous lenses. Exp. Eye Res. 45: 865–874.
Kern, H. L. and Ho, C. K. (1973a) Localization and specificity of the transport system for sugars in the calf lens. Exp. Eye Res. 15: 751–765.
Kern, H. L. and Ho, C. K. (1973b) Transport of L-glutamic acid and L-glutamine and their incorporation into lenticular glutathione. Exp. Eye Res. 17: 455–462.
Kinsey, V. E. and Reddy, D. V. N. (1965) Studies on the crystalline lens. XI. The relative role of the epithelium and capsule in transport. Invest. Ophthalmol. and Vis. Sci. 4: 104–116.
Kleiman, N. J., Wang, R., and Spector, A. (1990) Ultraviolet light induced DNA damage and repair in bovine lens epithelial cells. Curr. Eye Res. 9: 1185–1193.
Kondoh, H., Yasuda, K., and Okada, T. S. (1983) Tissue specific expression of a cloned chick δ-crystallin gene in mouse cells. Nature 301: 440–442.
Konofsky, K., Naumann, G. O. H., and Guggenmoos-Holtzmann, I. (1987) Cell density and sex chromatin in lens epithelium of human cataracts. Ophthalmol. 94: 875–880.
Krausz, E. et al. (1996) Expression of crystallins pax 6, filensin, CP49, MIP and MP20 in lens derived cell lines. Invest. Ophthalmol. and Vis. Sci. 37: 2120–2128.
Kuszak, J. R. (1995) The ultrastructure of epithelial and fiber cells in the crystalline lens. Intern. Rev. Cytol. 163: 305–350.
Kuszak, J. R. (1997) A re-examination of primate lens epithelial cell size, density and structure as a function of development, growth and age. Nova Acta Leopoldina 57: 45–66.
Lang, R. A. (1999) Which factors stimulate lens fiber cell differentiation in ûiûo? Invest. Ophthalmol. Vis. Res. 40: 3075–3078.
Lewis, W. H. (1904) Experimental studies on the development of the eye in amphibia. I. Origin of the lens Renu Palustris. Am. J. Anat. 3: 505–536.
Li, H. C., Yang, J. M., Jacobson, R., Pasko, D., and Sundin, O. (1994) Pax-6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. Dev. Biol. 162: 181–194.
Li, W. and Spector, A. (1996) Lens epithelial cell apoptosis is an early event in the development of UVBinduced cataract. Free Radical Biol. Med. 20: 301–311.
Li, W. C. et al. (1995a) Lens epithelial cell apoptosis appears to be a common cellular basis for noncongenital cataract development in humans and animals. J. Cell Biol. 130: 169–181.
Li, W. C., Kuszak, J. R., Wang, G. M., Wu, Z. Q., and Spector, A. (1995b) Calcimycin induced lens epithelial cell apoptosis contributes to cataract formation. Exp. Eye Res. 61: 91–98.
Lieska, N., Krotzer, K., and Yang, H. Y. (1992) A reassessment of protein synthesis by lens nuclear fiber cells. Exp. Eye Res. 54: 807–811.
Lin, L. R., Reddy, V. N., Giblin, F. J., Kador, P. F., and Kinoshita, J. H. (1990) Polyol accumulation in cultured human lens epithelial cells. Exp. Eye Res. 51: 93–100.
Lo, W. K. and Zhang, W. (1989) Endocytosis of macromolecules in the lenses of guinea pig and rabbit. Lens Eye Toxicity Res. 6: 603–612.
Lucas, V., Bassnet, S., Duncan, G., Stewart, S., and Gorghan, P. C. (1987) Membrane conductance and potassium permeability of the rat lens. Q. J. Exp. Physiol. 72: 81–93.
Mahon, K. A., Chepelinsky, A. B., Khillan, J. S., Overbeek, P. A., Piatigorsky, J., and Westphal, H. (1987) Oncogenesis of the lens in transgenic mice. Science 235: 1622–1628.
Marcantonio, J. M., Rakic, J. M., Vrensen, G. F. J. M., and Duncan, G. (2000) Lens cell populations studied in human donor capsular bags with implanted intraocular lenses. Invest. Ophthalmol. and Vis. Sci. 41: 1130–1141.
Mathias, R. T., Rae, J. L., and Baldo, G. J. (1997) Physiological properties of the normal lens. Physiol. Rev. 77: 21–50.
McAvovy, J. W. and Chamberlain, C. G. (1989) Fibroblast growth factor (FGF) induces different responses in lens epithelial cells depending on its concentration. Development 107: 221–228.
McAvovy, J. W. and Fernon, V. T. (1984) Neutral retains promote cell division and fibre differentiation in lens epithelial explants. Curr. Eye Res. 3: 827–834.
McAvovy, J. W. and Chamberlain, C. G. (1990) Growth factors in the eye. Progr. Growth Factor Res. 2: 29–43.
Menko, S., Philip, N., Veneziale, B., and Walker, J. (1988) Integrins and development: how might these receptors regulate differentiation of the lens. Ann. NY Acad. Sci. 15: 36–41.
Merriam, J. C. et al. (2000) An action spectrum for UV-B radiation and the rat lens. Invest. Ophthalmol. and Vis. Sci. 14: 2642–2647.
Merriam-Smith, R., Donaldson, P., and Kistler, J. (1999) Differential expression of facilitative glucose transporters GLUT1 and GLUT3 in the lens. Invest. Ophthalmol. and Vis. Sci. 40: 3224–3230.
Michael, R., Vrensen, G. F. J. M., van Marle, J., Gan, L., and Soderberg, P. G. (1998) Apoptosis in the rat lens after in ûiûo threshold dose ultraviolet irradiation. Invest. Ophthalmol. and Vis. Sci. 39: 2681–2687.
Mikulicih, A. G. and Young, R. W. (1963) Cell proliferation and displacement in the lens epithelium of young rats injected with tritiated thymidine. Invest. Ophthalmol. and Vis. Sci. 2: 344–354.
Mosley, A. E., Dean, W. L., and Delamere, N. A. (1996) K-ATPase in rat lens epithelium and fiber cell. Invest. Ophthalmol. and Vis. Sci. 37: 1502–1508.
Nagamoto, T., Eguchi, G., and Beebe, D. C. (2000) Alpha-smooth muscle actin expression in cultured lens epithelial cells. Invest. Ophthalmol. and Vis. Sci. 41: 1122–1129.
Nagineni, C. N. and Bhat, S. P. (1988) Maintenance of the synthesis of ?B-crystallin and progressive expression of ?Bp-crystallin in human fetal lens epithelial cells in culture. Dev. Biol. 130: 402–405.
Nagineni, C. N. and Bhat, S. P. (1989a) Human fetal lens epithelial cells in culture: an in vitro model for the study of crystallin expression and lens differentiation. Curr. Eye Res. 8: 285–291.
Nagineni, C. N. and Bhat, S. P. (1989b) ?B-crystallin is expressed in kidney epithelial cell lines and not in fibroblasts. FEBS Lett. 249: 89–94.
Nagineni, C. N. and Bhat, S. P. (1992) Lens fiber cell differentiation and expression of crystallins in cocultures of human fetal lens epithelial cells and fibroblasts. Exp. Eye Res. 54: 193–200.
Okada, T. S., Eguchi, G., and Takeichi, M. (1971) The expression of differentiation of chicken lens epithelium in in vitro cell culture. Dev. Growth Differentiation 13: 323–336.
Ogini, H. and Yasuda, K. (1998) Induction of lens differentiation by activation of a ?ZIP transcription factor. L-Maf. Science 280: 115–118.
Padgoankar, V. A., Giblin, F. J., Fowler, K., Leverenz, V. R., Reddan, J. R., and Dziedzic, D. C. (1997) Heme oxygenase synthesis is induced in cultured lens epithelium by hypobaric oxygen or puromycin. Exp. Eye Res. 65: 435–443.
Parekh, A. B. and Penner, R. (1997) Store depletion and calcium influx. Physiol. Rev. 77: 901–930.
Paterson, C. A. (1972) Distribution and movement of ions in the ocular lens. Document. Ophthalmol. 31: 1–28.
Perry, M. M., Tassin, J., and Courtois, Y. A. (1979) Comparison of human lens epithelial cells in situ and in vitro in relation to aging: an ultra structural study. Exp. Eye Res. 28: 327–341.
Piatigorsky, J. (1981) Lens differentiation in vertebrates: A review of cellular and molecular features. Differentiation 19: 134–152.
Piper, H. M., Spahr, R., Krutzfeldt, A., Siegmund, B., Schwartz, P., and Pau, H. (1990) Changes in the energy metabolism of cultured lens epithelial cells in comparison with the fresh lens. Exp. Eye Res. 51: 131–138.
Pirie, A. (1965) Glutathione peroxidase in lens and a source of hydrogen peroxide in the aqueous humor. Biochem. J. 96: 244–253.
Rae, J. L., Bartling, C., Rae, J., and Mathias, R. T. (1996) Dye transfer between cells of the lens. Membrane Biol. 150: 89–103.
Rae, J. L. and Shephard, A. R. (2000) Kv3.3 potassium, channels in lens epithelium and corneal endothelium. Exp. Eye Res. 70: 339–348.
Rae, J. and Shephard, A. R. (1996) Molecular biology and electrophysiology of calcium-activated channels from lens epithelium. Curr. Eye Res. 17: 264–275.
Raff, M. C., Barres, B. A., Burne, J. F., Coles, H. S., Ishizaki, Y., and Jacobson, M. D. (1993) Programmed cell death and the control of cell survival: Lessons from the nervous system. Science 262: 695–700.
Rafferty, N. S., Scholtz, D. I., Goldberg, M., and Lewckyj, M. (1990) Immunocytochemical evidence for an actin-myosin system in the lens epithelial cells. Exp. Eye Res. 51: 591–600.
Ramamoorthy, S., Del Monte, M. A., Leibach, F. H., and Ganapathy, V. (1994) Molecular identity and calmodulin-mediated regulation of the taurine transporter in a human retinal pigment epithelial cell line. Curr. Eye Res. 13: 523–529.
Reddan, J. R. et al. (1981) Donor age influences the growth of rabbit lens epithelial cells in vitro. Vision Res. 21: 11–23.
Reddy, V. N. (2000) A forty-two year voyage through vision research. J. Ocular Pharmacol. Therapeut. 16: 97–107.
Reddy, D. V. N., Klethi, J., and Kinsey, V. E. (1966) Studies on the crystalline lens XII. Turnover of glycine and glutamic acid in glutathione and ophthalmic acid in the rabbit. Invest. Ophthalmol. and Vis. Sci. 5: 594–600.
Reddy, G. B. and Bhat, K. S. (1998) UV-B irradiation alters the activities and kinetic properties of the enzymes of energy metabolism in rat lens during aging. J. Photochem. Photobiol. B42: 40–46.
Reddy, V. N., Giblin, F. J., and Matsuda, H. (1980) Defense systems of the lens against oxidative damage. In: Red Blood Cell and Lens Metabolism ( Srivastava, S., ed.), Elsevier, North Holland, pp. 139–154.
Reddy, V. N., Schwass, D., Chakrapani, B., and Lim, C. P. (1976) Biochemical changes associated with the development and reversal of galactose cataracts. Exp. Eye Res. 23: 483–493.
Ringens, P., Mungyer, G., Jap, P., Ramaekers, F., Hoenders, H., and Bloemendal, H. (1982) Exp. Eye Res. 35: 313–324.
Robinson, K. R. and Patterson, J. W. (1983) Localization of steady currents in the lens. Curr. Eye Res. 2: 843–847.
Robinson Jr., W. G., Holder, N., and Kinoshita, J. H. (1990) Role of lens epithelium in sugar cataract formation. Exp. Eye Res. 50: 641–646.
Robinson, M. L., Overbeek, P. A., and Verran, D. J. (1995) Extracellular FGF-1 acts as a lens differentiation factor in transgenic mice. Development 121: 505–514.
Saha, M. S. et al. (1989) Embryonic lens induction: More than meets the optic vesicle. Cell Diff. Dev. 28: 153–171.
Sasaki, H., Lin, L. R., Yokoyama, T., Sevilla, M. D., Reddy, V. N., and Giblin, F. J. (1998) TEMPOL protects against lens DNA strand breaks and cataract in the X-rayed rabbit. Invest. Ophthalmol. and Vis. Sci. 39: 544–552.
Sawhney, R. S. (1995) Identification of SPARC in the anterior lens capsule and its expression by lens epithelial cells. Exp. Eye Res. 61: 645–648.
Sax, C. M., Dziedzic, D. C., Piatigorsky, J., and Reddan, J. R. (1995) Analysis of a-crystallin expression in cultured mouse and rabbit lens cells. Exp. Eye Res. 61: 125–127.
Sax, C. M. and Piatigorsky, J. (1994) Expression of the alpha-crystallin_small heat-shock protein_molecular chaperone genes in the lens and other tissues. Adv. Enzymol. Related Areas of Mol. Biol. 69: 155–201.
Shang, F., Gong, X., and Taylor, A. (1997) Activity of ubiquitin-dependent pathway in response to oxidative stress. Ubiquitin-activating enzyme is transiently up regulated. J. Biol. Chem. 272: 23086–23093.
Shui, Y. B. et al. (2000) Morphological observations on cell death and phagocytosis induced by ultraviolet irradiation in a cultured human lens epithelial cell line. Exp. Eye Res. 71: 609–618.
Sidjanin, D., Zigman, S., and Reddan, J. (1993) DNA damage and repair in rabbit lens epithelial cells following UVA irradiation. Curr. Eye Res. 12: 773–781.
Simonneau, L., Herve, B., Jacquemin, E., and Courtois, Y. (1983) State of differentiation of bovine epithelial lens cells in ûitro. Relationship between the variation of the cell shape and the synthesis of crystallins. Cell Differ. 13: 185–190.
Singh, D. P. et al. (2000) Lens epithelium derived growth factor LEDGF: Effects on growth and survival factor of lens epithelial cell, keratinocytes and fibroblasts. Biochem. Biophys. Res. Commun. 267: 371–381.
Spector, A. (1995) Oxidative stress-induced cataract: mechanism of action. FASEB J. 9: 1173–1182.
Spector, A., Wang, R. R., Ma, W., and Kleiman, N. J. (2000) Development and characterization of and H?O?-resistant immortal lens epithelial cell line. Invest. Ophthalmol. and Vis. Sci. 41: 832–843.
Spemann, H. (1901) Uber korrelation in der entwickling des auges. Verh. Anat. Ges. 15: 61–79.
Spemann, H. (ed.) (1962) Embryonic Deûelopment and Induction. New York, Hafner Publishing.
Srivastava, S. K., Singhal, S. S., Awasthi, S., Pikuka, S., Ansari, N. H., and Awasthi, Y. C. (1996) A glutathione S-transferase isozyme (bGST5.8) involved in the metabolism of 4-hydroxy-2-transnonenal is localized in bovine lens epithelium. Exp. Eye Res. 63: 329–337.
Starka, L., Hampl, R., Obenberger, J., and Doskocil, M. (1986) The role of corticosteroids in the homeostasis of the eye. J. Steroid Biochem. 24: 199–205.
Stellar, H. (1995) Mechanisms and genes of cellular suicide. Science 267: 1445–1449.
Stokes, J. et al. (2000) Distribution of glucocorticoid and mineralcorticoid receptors and 11 β-hydroxysteroid dehydrogenases in human and rat ocular tissues. Invest. Ophthalmol. and Vis. Sci. 41: 1629–1638.
Straatsma, B. R., Lightfoot, D. O., Brake, R. M., Horwits, J. (1991) Lens capsule and epithelium in agerelated cataract. Am. J. Ophthalmol. 112: 283–296.
Struck, H. G., Hieder, C., and Lautenschlager, C. (2000) Veranderungen des linsenepithels bei diabetikern und nichtdiabetikern mit verschiedenen trubungsformen einer altersassoziierten katarakt. Klin. Monatsbl. Augenheilkd 216: 204–209.
Sun, K. J., Iwata, T., Zigler Jr., J. S., and Carper, D. A. (2000) Differential gene expression in male and female rat lenses undergoing cataract by transforming growth factor-beta (TGF-beta). Exp. Eye Res. 70: 169–181.
Tassin, J., Malaise, E., and Courtois, Y. (1979) Human lens cells have in ûitro proliferation capacity inversely proportional to the donor age. Exp. Cell Res. 123: 388–392.
Tung, W., Chylack, L., and Andley, U. (1988) Lens hexokinase deactivation by near-UV irradiation. Curr. Eye Res. 7: 257–263.
Vasavada, A. R., Cherian, M., Yadav, S., and Rawal, U. M. (1991) Lens epithelial cell density and histomorphological study in cataractous lenses. J. Cataract Refract. Surg. 17: 798–804.
Van Venrooji, W. J., Groenevald, A. A., Bloemendal, H., and Beneditti, E. L. (1974) Cultured calf lens epithelium. 1. Methods of cultivation and characteristics of the cultures. Exp. Eye Res. 18: 517–526.
Vaziri, H. et al. (1999) Analysis of genomic integrity and p53-dependent G1 checkpoint in Telomeraseinduced extended-life span human fibroblasts. Mol. Cell Biol. 19: 2373–2379.
Vaulont, S., Vasseur-Cognet, M., and Kahn, A. (2000) Glucose regulation of gene transcription. J. Biol. Chem. 275: 31555–31558.
Vermorken, A. J., Groenevald, A. A., Hilderink, J. M. H. C., de Waal, R., and Bloemendal, H. (1977) Dedifferentiation of lens epithelial cells in tissue culture. Mol. Biol. Rep. 3: 371–378.
Vishwanath, R. I. et al. (1999) The transcriptional program in the response of human fibroblasts to serum. Science 283: 83–867.
Wen, Y., Li, G. W., Chen, P., Wong, E., and Bekhor, I. (1995) Lens epithelial cell mRNA. II. Expression of a mRNA encoding a lipid-binding protein in rat lens epithelial cells. Gene 158: 269–274.
Wintour, E. M. (1997) Water channels and urea transporters. Clin. Exp. Pharmacol. Physiol. 24: 1–9.
Worgul, B. V. et al. (1991) Evidence of genotoxic damage in human cataractous lenses. Mutagenesis 6: 495–499.
Worgul, B. V., Merriam Jr., G. R., and Medvedovsky, C. (1989) Cortical cataract development-an expression of primary damage to the lens epithelium. Lens Eye Toxic Res. 6: 559–571.
Wormstone, I. M., Liu, C. S. C., Rakic, J. M., Mercantonio, J. M., Vrensen, G. F. J. M., and Duncan, G. (1997) Human lens epithelial cell proliferation in a protein-free medium. Invest. Ophthalmol. and Vis. Sci. 38: 396–404.
Wormstone, I. M., Tamiya, S., Mercantonio, J. M., and Reddan, J. R. (2000) Hepatocyte growth factor function and c-Met expression in human lens epithelial cells. Invest. Ophthalmol. and Vis. Sci. 41: 4216–4222.
Wride, M. A. and Saunders, E. J. (1998) Nuclear degeneration in the developing lens and its regulation by TNF-α. Exp. Eye Res. 66: 371–383.
Yan Q., Clark, J. I., and Sage, E. H. (2000) Expression and characterization of SPARC in human lens and in the aqueous and vitreous humors. Exp. Eye Res. 71: 81–90.
Zampighi, G. A., Eskandari, S., and Kremen, M. (2000) Epithelial organization of the mammalian lens. Exp. Eye Res. 71: 415–435.
Zelenka, P. S., Gao, C. Y., Rampalli, A., Arora, J., Chauthaiwale, V., and He, H. Y. (1997) Cell cycle regulation in the lens: Proliferation, quiescence, apoptosis and differentiation. Prog. Ret. Eye Res. 16: 303–322.
Zhou, C. and Cammarata, P. R. (1997) Cloning the bovine NaC_myoinositol cotransporter gene and characterization of an osmotic responsive promoter. Exp. Eye Res. 65: 349–363.
Zigman, S. (2000) Lens UV photobiology. J. Ocular Pharmacol. Therapeutics 16: 161–165.
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Bhat, S.P. The Ocular Lens Epithelium. Biosci Rep 21, 537–563 (2001). https://doi.org/10.1023/A:1017952128502
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DOI: https://doi.org/10.1023/A:1017952128502