Abstract
The function of the cytoskeleton in lens was first considered when cytoplasmic microtubules were observed in elongating fibre cells of the chick lens nearly 40 years ago.1 Since that time, tubulin, actin, vimentin and intermediate filaments have been identified and found to function in mitosis, motility and cellular morphology during lens cell differentiation.2-10 A role for the cytoskeleton in accommodation has been proposed3,8,9 and modification of the cytoskeletal proteins has been observed in several cataract models.4,11-21 Recently, a progressive increase in protein aggregation and lens opacification was found to correspond with the loss of cytoskeletal protein in the selenite model for cataract.22 In the present report a model is proposed for the role of tubulin, actin, vimentin, spectrin and the lens-specific filaments, filensin and CP49, in the establishment and maintenance of transparent lens cell structure.
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References
Byers B, Porter KR . Oriented microtubules in elongating cells of the developing lens rudiment after induction. Proc Natl Acad Sci USA 1964;52:1091–9.
Ireland M, Maisel H, Bradley RH . The rabbit lens cytoskeleton: an ultrasound analysis. Ophthalmic Res 1978;10:231–6.
Ramaekers FC, Poels LG, Jap PH, Bloemendal H . Simultaneous demonstration of microfilaments and intermediate-sized filaments in the lens by double immunofluorescence. Exp Eye Res 1982;35:363–9.
Prescott AR, Stewart S, Duncan G, Gowing R, Warn RM . Diamide induces reversible changes in morphology, cytoskeleton and cell-cell coupling in lens epithelial cells. Exp Eye Res 1991;52:83–92.
Spudich JA, ed. The cytoskeleton. Palo Alto, CA: Annual Reviews, 1996.
Lo WK, Shaw AP, Wen XJ . Actin filament bundles in cortical fiber cells of the rat lens. Exp Eye Res 1997;65:691–701.
Mousa GY, Trevithick JR . Actin in the lens: changes in actin during differentiation of lens epithelial cells in vivo. Exp Eye Res 1979;29:71–81.
Kibbelaar MA, Ramaekers FC, Ringens PJ, Selten-Versteegen AM, Poels LG, Jap PH, et al. Is actin in eye lens a possible factor in visual accommodation? Nature 1980;285:506–8.
Rafferty NS, Scholz DL, Goldberg M, Lewyckyj M . Immunocytochemical evidence for an actin-myosin system in lens epithelial cells. Exp Eye Res 1990;;51591–600.
Sandilands A, Prescott AR, Carter JM, Hutcheson AM, Quinlan RA, Richards J, FitzGerald PG . Vimentin and CP49/filensin form distinct networks in the lens which are independently modulated during lens fibre cell differentiation. J Cell Sci 1995;108:1397–406.
Mousa GY, Creighton MO, Trevithick JR . Eye lens opacity in cortical cataracts associated with actin-related globular degeneration. Exp Eye Res 1979;29:379–91.
Tagliavini J, Gandolfi SA, Maraini G . Cytoskeleton abnormalities in human senile cataract. Curr Eye Res 1986;5:903–10.
Capetanaki Y, Smith S, Heath JP . Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation. J Cell Biol 1989;109:1653–64.
Truscott RJ, Marcantonio JM, Tomlinson J, Duncan G . Calcium-induced opacification and proteolysis in the intact rat lens. Invest Ophthalmol Vis Sci 1990;31:2405–11.
Bloemendal H . Proctor lecture. Disorganisation of membranes and abnormal intermediate filament assembly lead to cataract. Invest Ophthalmol Vis Sci 1991;32:445–55.
Calvin HI, Patel SA, Zhang JP, Li MY, Fu SC . Progressive modifications of mouse lens crystallins in cataracts induced by buthionine sulfoximine. Exp Eye Res 1992;54:611–9.
Inomata M, Nomura K, Takehana M, Saido TC, Kawashima S, Shumiya S . Evidence for the involvement of calpain in cataractogenesis in Shumiya cataract rat (SCR). Biochim Biophys Acta 1997;1362:11–23.
Onishi T, Sato T, Yaguchi S, Ogino T, Oniki H, Nakano K, et al. Ultrastructural study of lens in rat hereditary cataract by quick-freezing and deep-etching. Nippon Ganka Gakkai Zasshi 1997;101:312–7.
Tumminia SJ, Jonak GJ, Focht RJ, Cheng YS, Russell P . Cataractogenesis in transgenic mice containing the HIV-1 protease linked to the lens alpha A-crystallin promoter. J Biol Chem 1996;271:425–31.
Rafferty NS, Rafferty KA, Zigman S . Comparative response to UV irradiation of cytoskeletal elements in rabbit and skate lens epithelial cells. Curr Eye Res 1997;16:310–9.
Clement S, Velasco PT, Murthy SN, Wilson JH, Lukas TJ, Goldman RD, Lorand L . The intermediate filament protein, vimentin, in the lens is a target for cross-linking by transglutaminase. J Biol Chem 1998;273:7604–9.
Matsushima H, David LL, Hiraoka T, Clark JI . Loss of cytoskeletal proteins and lens cell opacification in the selenite cataract model. Exp Eye Res 1997;64:387–95.
Brewitt B, Clark JI . Growth and transparency in the lens, an epithelial tissue, stimulated by pulses of PDGF. Science 1988;242:777–9.
Brewitt B, Talian JC, Zelenka PS . Cell cycle synchrony in the developing chicken lens epithelium. Dev Biol 1992;152:315–22.
Kuszak JR, Peterson KL, Brown HG . Electron microscopic observations of the crystalline lens. Microsc Res Tech 1996;33:441–79.
Taylor VL, al-Ghoul KJ, Lane CW, Davis VA, Kuszak JR, Costello MJ . Morphology of the normal human lens. Invest Ophthalmol Vis Sci 1996;37:1396–410.
Zelenka PS, Gao C-Y, Rampalli A, Arora J, Chauthaiwale V, He H-Y . Cell cycle regulation in the lens: proliferation, quiescence, apoptosis and differentiation. Prog Retinal Eye Res 1997;16:303–22.
Kuwabara T, Imaizumi M . Denucleation process of the lens. Invest Ophthalmol 1974;13:973–81.
Piatigorsky J . Lens differentiation in vertebrates: a review of cellular and molecular features. Differentiation 1981;19:134–53.
Bassnett S, Beebe DC . Coincident loss of mitochondria and nuclei during lens fiber cell differentiation. Dev Dyn 1992;194:85–93.
McAvoy JW . Cell division, cell elongation and the coordination of crystallin gene expression during lens morphogenesis in the rat. J Embryol Exp Morphol 1978;45:271–81.
McAvoy JW . Cell division, cell elongation and distribution of alpha-, beta- and gamma-crystallins in the rat lens. J Embryol Exp Morphol 1978;44:149–65.
Clark JI, Benedek GB . Phase diagram for cell cytoplasm from the calf lens. Biochem Biophys Res Commun 1980;95:482–9.
Clark JI . Lens cytoplasmic protein solutions: analysis of a biologically occurring aqueous phase separation. Methods Enzymol 1994;228:525–37.
Hiraoka T, Clark JI, Li XY, Thurston GM . Effect of selected anti-cataract agents on opacification in the selenite cataract model. Exp Eye Res 1996;62:11–9.
Clark JI . Phase separation and hydrogen bonding in cells of the ocular lens. Biopolymers 1990;30:995–9.
Benedek GB . Theory of transparency of the eye. Appl Optics 1971;10:459–71.
Delaye M, Clark JI, Benedek GB . Coexistence curves for the phase separation in the calf lens cytoplasm. Biochem Biophys Res Commun 1981;100:908–14.
Delaye M, Clark JI, Benedek GB . Identification of the scattering elements responsible for lens opacification in cold cataracts. Biophys J 1982;37:647–56.
Delaye M, Tardieu A . Short-range order of crystallin proteins accounts for eye lens transparency. Nature 1983;302:415–7.
Bettelheim FA . Physical basis of lens transparency. In: Maisel H, ed. The ocular lens. New York: Marcel Dekker, 1985:265–99.
Bloemendahl H, ed. Molecular and cellular biology of the eye lens. New York: Wiley, 1981.
Ireland M, Maisel H . A cytoskeletal protein unique to lens fiber cell differentiation. Exp Eye Res 1984;38:637–45.
Maisel H . The ocular lens. New York: Marcel Dekker, 1985.
Sandilands A, Prescott AR, Hutcheson AM, Quinlan RA, Casselman JT, FitzGerald PG . Filensin is proteolytically processed during lens fiber cell differentiation by multiple independent pathways. Eur J Cell Biol 1995;67:238–53.
Siew EL, Bettelheim FA . Light scattering parameters of rat lenses with calcium-induced cataracts. Exp Eye Res 1996;62:265–70.
Marcantonio JM, Duncan G . Calcium-induced degradation of the lens cytoskeleton. Biochem Soc Trans 1991;19:1148–50.
Vrensen GF, Graw J, De Wolf A . Nuclear breakdown during terminal differentiation of primary lens fibres in mice: a transmission electron microscopic study. Exp Eye Res 1991;52:647–59.
David LL, Azuma M, Shearer TR . Cataract and the acceleration of calpain-induced beta-crystallin insolubilization occurring during normal maturation of rat lens. Invest Ophthalmol Vis Sci 1994;35:785–93.
Dahm R, Gribbon C, Quinlan RA, Prescott AR . Lens cell organelle loss during differentiation versus stress-induced apoptotic changes. Biochem Soc Trans 1997;25:S584.
Azuma M, Fukiage C, David LL, Shearer TR . Activation of calpain in lens: a review and proposed mechanism. Exp Eye Res 1997;64:529–38.
David LL, Shearer TR . Beta-crystallins insolubilized by calpain II in vitro contain cleavage sites similar to beta-crystallins insolubilized during cataract. FEBS Lett 1993;324:265–70.
Hiraoka T, Clark JI . Inhibition of lens opacification during the early stages of cataract formation. Invest Ophthalmol Vis Sci 1995;36:2550–5.
Shearer TR, Ma H, Fukiage C, Azuma M . Selenite nuclear cataract: review of the model. Mol Vis 1997;3:8.
Quinlan R, Hutchison C, Lane B . Intermediate filament proteins. Protein Profile 1994;1:779–911.
David LL, Shearer TR . Calcium-activated proteolysis in the lens nucleus during selenite cataractogenesis. Invest Ophthalmol Vis Sci 1984;25:1275–83.
Shearer TR, David LL, Anderson RS, Azuma M . Review of selenite cataract. Curr Eye Res 1992;11:357–69.
Yoshida H, Murachi T, Tsukahara I . Degradation of actin and vimentin by calpain II, a Ca2+-dependent cysteine proteinase, in bovine lens. FEBS Lett 1984;170:259–62.
Yoshida H, Murachi T, Tsukahara I . Limited proteolysis of bovine lens alpha-crystallin by calpain, a Ca2+-dependent cystein proteinase, isolated from the same tissue. Biochim Biophys Acta 1984;798:252–9.
Sanderson J, Marcantonio JM, Duncan G . Calcium ionophore induced proteolysis and cataract; inhibition by cell permeable calpain antagonists. Biochem Biophys Res Commun 1996;218:893–901.
Clark JI, Steele JE . Phase-separation inhibitors and prevention of selenite cataract. Proc Natl Acad Sci USA 1992;89:1720–4.
Clark JI, Livesey JC, Steele JE . Phase separation inhibitors and lens transparency. Optom Vis Sci 1993;70:873–9.
Clark JI, Livesey JC, Steele JE . Delay or inhibition or rat lens opacification using pantethine and WR-77913. Exp Eye Res 1996;62:75–84.
Ishimoto C, Sun S-T, Nishio I, Goalwin P, Tanaka T . Cytoplasmic phase separation in galactosemic cataracts in lenses of young rats. Proc Natl Acad Sci USA 1979;76:4414–6.
Harding JJ . Cataract: biochemistry, epidemiology and pharmacology. London: Chapman & Hall, 1991.
FitzGerald PG, Graham D . Ultrastructural localization of alpha A-crystallin to the bovine lens fiber cell cytoskeleton. Curr Eye Res 1991;10:417–36.
Leach IH, Tsang ML, Church RJ, Lowe J . Alpha-B crystallin in the normal human myocardium and cardiac conducting system. J Pathol 1994;173:255–60.
Nicholl ID, Quinlan RA . Chaperone activity of alpha-crystallins modulates intermediate filament assembly. EMBO J 1994;13:945–53.
Carter JM, Hutcheson AM, Quinlan RA . In vitro studies on the assembly properties of the lens proteins CP49, CP115: coassembly with alpha-crystallin but not with vimentin. Exp Eye Res 1995;60:181–92.
Wang K, Spector A . Alpha-crystallin stabilizes actin filaments and prevents cytochalasin-induced depolymerization in a phosphorylation-dependent manner. Eur J Biochem 1996;242:56–66.
Wisniewski T, Goldman JE . Alpha B-crystallin is associated with intermediate filaments in astrocytoma cells. Neurochem Res 1998;23:385–92.
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Clark, J., Clark, J., David, L. et al. Lens cytoskeleton and transparency: A model. Eye 13, 417–424 (1999). https://doi.org/10.1038/eye.1999.116
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DOI: https://doi.org/10.1038/eye.1999.116
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