The Lens Circulation

The lens is the largest organ in the body that lacks a vasculature. The reason is simple: blood vessels scatter and absorb light while the physiological role of the lens is to be transparent so it can assist the cornea in focusing light on the retina. We hypothesize this lack of blood supply has led the lens to evolve an internal circulation of ions that is coupled to fluid movement, thus creating an internal micro-circulatory system, which makes up for the lack of vasculature. This review covers the membrane transport systems that are believed to generate and direct this internal circulatory system.

[1]  J. Kistler,et al.  Identification of a 70,000-D protein in lens membrane junctional domains , 1985, The Journal of cell biology.

[2]  J. Rae,et al.  Whole-cell currents from noncultured human lens epithelium. , 1992, Investigative Ophthalmology and Visual Science.

[3]  N. Gilula,et al.  Gap junctional coupling in lenses lacking alpha3 connexin. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Kistler,et al.  Protein processing in lens intercellular junctions: cleavage of MP70 to MP38. , 1987, Investigative ophthalmology & visual science.

[5]  J. Rae,et al.  Kv3.3 potassium channels in lens epithelium and corneal endothelium. , 2000, Experimental eye research.

[6]  V. Reddy,et al.  Glutathione and its function in the lens--an overview. , 1990, Experimental eye research.

[7]  G. Zampighi,et al.  Epithelial organization of the mammalian lens. , 2000, Experimental eye research.

[8]  T. W. White,et al.  Connections Between Connexins, Calcium, and Cataracts in the Lens , 2004, The Journal of general physiology.

[9]  P. Donaldson,et al.  Expression patterns for glucose transporters GLUT1 and GLUT3 in the normal rat lens and in models of diabetic cataract. , 2003, Investigative ophthalmology & visual science.

[10]  K. Schey,et al.  Post-translational modifications of aquaporin 0 (AQP0) in the normal human lens: spatial and temporal occurrence. , 2004, Biochemistry.

[11]  J. Rae,et al.  Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family. , 1998, Experimental eye research.

[12]  M. Lou.  Redox regulation in the lens , 2003, Progress in Retinal and Eye Research.

[13]  D. Eaton,et al.  Differential effect of cyanohydroxybutene on glutathione synthesis in liver and pancreas of male rats. , 1993, Toxicology and applied pharmacology.

[14]  C. Sellitto,et al.  Lens gap junctional coupling is modulated by connexin identity and the locus of gene expression. , 2004, Investigative ophthalmology & visual science.

[15]  G. McBean.  Cerebral cystine uptake: a tale of two transporters. , 2002, TIPS - Trends in Pharmacological Sciences.

[16]  K. Sweadner.  Isozymes of the Na+/K+-ATPase. , 1989, Biochimica et biophysica acta.

[17]  B. Zlokovic,et al.  Low de novo glutathione synthesis from circulating sulfur amino acids in the lens epithelium. , 1997, Experimental eye research.

[18]  R. Mathias,et al.  Regulation of aquaporin water permeability in the lens. , 2005, Investigative ophthalmology & visual science.

[19]  A. Prescott,et al.  Gap junctions containing alpha8-connexin (MP70) in the adult mammalian lens epithelium suggests a re-evaluation of its role in the lens. , 1999, Experimental eye research.

[20]  N. Delamere,et al.  Expression, regulation and function of Na,K-ATPase in the lens , 2004, Progress in Retinal and Eye Research.

[21]  C. Higgins,et al.  Cell volume regulation and swelling-activated chloride channels. , 2003, Biochimica et biophysica acta.

[22]  P. Donaldson,et al.  Molecular characterization of the cystine/glutamate exchanger and the excitatory amino acid transporters in the rat lens. , 2005, Investigative ophthalmology & visual science.

[23]  S. Fleischer,et al.  Heterogeneity of Ca2+ gating of skeletal muscle and cardiac ryanodine receptors. , 1997, Biophysical journal.

[24]  J. Rae,et al.  Electrically silent potassium channel subunits from human lens epithelium. , 1999, The American journal of physiology.

[25]  P. Donaldson,et al.  Roles for KCC transporters in the maintenance of lens transparency. , 2006, Investigative ophthalmology & visual science.

[26]  P. Donaldson,et al.  Molecular solutions to mammalian lens transparency. , 2001, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[27]  J. T. Parmelee.  Measurement of steady currents around the frog lens. , 1986, Experimental eye research.

[28]  M. Niemeyer,et al.  K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart. , 2001, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[29]  M. Tunstall,et al.  Localised Fibre Cell Swelling Characteristic of Diabetic Cataract Can Be Induced in Normal Rat Lens Using the Chloride Channel Blocker 5-Nitro-2-(3-Phenylpropylamino) Benzoic Acid , 1999, Ophthalmic Research.

[30]  E. Beutler.  Nutritional and metabolic aspects of glutathione. , 1989, Annual review of nutrition.

[31]  P. Agre,et al.  Water Channel Properties of Major Intrinsic Protein of Lens (*) , 1995, The Journal of Biological Chemistry.

[32]  D. Goodenough,et al.  Lens metabolic cooperation: a study of mouse lens transport and permeability visualized with freeze-substitution autoradiography and electron microscopy , 1980, The Journal of cell biology.

[33]  T. W. White,et al.  Intercellular Communication in Lens Development and Disease , 2005 .

[34]  C. Paterson,et al.  Chloride concentration and exchange in rabbit lens. , 1971, Experimental Eye Research.

[35]  R. Wymore,et al.  Isoform-Specific Function and Distribution of Na/K Pumps in the Frog Lens Epithelium , 2000, The Journal of Membrane Biology.

[36]  R. Mathias,et al.  Isoform-Specific Regulation of the Na(+)-K(+) Pump in Heart. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[37]  J L Rae,et al.  Electrical properties of structural components of the crystalline lens. , 1979, Biophysical journal.

[38]  Potassium currents from isolated frog lens epithelial cells. , 1992, Experimental eye research.

[39]  C. Soeller,et al.  Functional imaging: New views on lens structure and function , 2004, Clinical and experimental pharmacology & physiology.

[40]  N. Gilula,et al.  Gap junctional coupling in lenses lacking α3 connexin , 1998 .

[41]  S. Harrison,et al.  Lipid–protein interactions in double-layered two-dimensional AQP0 crystals , 2005, Nature.

[42]  R. Mathias,et al.  Local Osmosis and Isotonic Transport , 2005, The Journal of Membrane Biology.

[43]  C. Paterson.  Distribution and movement of ions in the ocular lens , 1972, Documenta Ophthalmologica.

[44]  K. Cooper,et al.  Inwardly rectifying potassium current in mammalian lens epithelial cells. , 1991, The American journal of physiology.

[45]  J. Rae,et al.  Ion transporters and receptors in cDNA libraries from lens and cornea epithelia. , 1998, Current eye research.

[46]  A. Le,et al.  A novel role for FGF and extracellular signal–regulated kinase in gap junction–mediated intercellular communication in the lens , 2001, The Journal of cell biology.

[47]  A. S. Menko,et al.  Lens epithelial cell differentiation. , 2002 .

[48]  Christian Soeller,et al.  Gap junction processing and redistribution revealed by quantitative optical measurements of connexin46 epitopes in the lens. , 2004, Investigative ophthalmology & visual science.

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

[50]  J. Rae,et al.  Kir2.1 Potassium channels and corneal epithelia , 2000 .

[51]  R. Mathias,et al.  Transport properties of the lens. , 1985, The American journal of physiology.

[52]  A. Peskoff.  Electric potential in cylindrical syncytia and muscle fibers. , 1979, Bulletin of mathematical biology.

[53]  S. Bassnett.  Lens organelle degradation. , 2002, Experimental eye research.

[54]  Jean X. Jiang,et al.  Regulation of Lens Connexin 45.6 by Apoptotic Protease, Caspase-3 , 2001, Cell communication & adhesion.

[55]  C. Kushmerick,et al.  Ion, water and neutral solute transport in Xenopus oocytes expressing frog lens MIP. , 1995, Experimental eye research.

[56]  James E. Hall,et al.  pH and Calcium Regulate the Water Permeability of Aquaporin 0* , 2000, The Journal of Biological Chemistry.

[57]  James E. Hall,et al.  Molecular Basis of pH and Ca2+ Regulation of Aquaporin Water Permeability , 2004, The Journal of general physiology.

[58]  N. Gilula,et al.  Gap Junctional Coupling in Lenses from α8 Connexin Knockout Mice , 2001, The Journal of general physiology.

[59]  R. Mathias,et al.  Spatial variations in membrane properties in the intact rat lens. , 1992, Biophysical journal.

[60]  J. Horwitz,et al.  Catalytic subunit isoforms of mammalian lens Na,K-ATPase. , 1994, Current eye research.

[61]  J. Kuszak,et al.  Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice , 2001 .

[62]  E. Beyer,et al.  Characterization of the gap junction protein connexin56 in the chicken lens by immunofluorescence and immunoblotting. , 1994, Investigative ophthalmology & visual science.

[63]  K. Cooper,et al.  Electrophysiology of cultured human lens epithelial cells , 1990, The Journal of Membrane Biology.

[64]  T. Gonen,et al.  Aquaporin-0 membrane junctions form upon proteolytic cleavage. , 2004, Journal of molecular biology.

[65]  J. Rae,et al.  Molecular biology and electrophysiology of calcium-activated potassium channels from lens epithelium. , 1998, Current eye research.

[66]  P. Donaldson,et al.  Molecular identification and characterisation of the glycine transporter (GLYT1) and the glutamine/glutamate transporter (ASCT2) in the rat lens. , 2006, Experimental eye research.

[67]  H. Rosskothen,et al.  Transport of fluid by lens epithelium. , 1999, The American journal of physiology.

[68]  Y. Kanai,et al.  Cloning and Functional Characterization of a System ASC-like Na+-dependent Neutral Amino Acid Transporter* , 1996, The Journal of Biological Chemistry.

[69]  P. Donaldson,et al.  Processing of the gap junction protein connexin50 in the ocular lens is accomplished by calpain. , 1997, European journal of cell biology.

[70]  Jean X. Jiang,et al.  The Development-associated Cleavage of Lens Connexin 45.6 by Caspase-3-like Protease Is Regulated by Casein Kinase II-mediated Phosphorylation* , 2001, The Journal of Biological Chemistry.

[71]  R. Mathias.  Effect of tortuous extracellular pathways on resistance measurements. , 1983, Biophysical journal.

[72]  N. Dohn,et al.  Volume Regulation in Red Blood Cells , 1998 .

[73]  L. Ebihara.  New roles for connexons. , 2003, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[74]  B. Fanburg,et al.  Regulation of cellular glutathione. , 1989, The American journal of physiology.

[75]  R. Mathias,et al.  The localization of transport properties in the frog lens. , 1985, Biophysical journal.

[76]  J. Rae,et al.  Kir2.1 Potassium channels and corneal epithelia. , 2000, Current eye research.

[77]  H. Bloemendal.  Molecular and cellular biology of the eye lens , 1981 .

[78]  Kevin F Webb.  Spatial variations in the membrane properties of differentiating fibre cells isolated from the rat lens. , 2006 .

[79]  J. Patterson.  Volume regulation in rat lenses in media with varying concentrations of potassium and sodium. , 1983, Experimental eye research.

[80]  A. Schousboe,et al.  High affinity glutamate transporters: regulation of expression and activity. , 1997, Molecular pharmacology.

[81]  J. Patterson,et al.  Localization of steady currents in the lens. , 1982, Current eye research.

[82]  James E. Hall,et al.  AQP 0-LTR of the CatFr mouse alters water permeability and calcium regulation of wild type AQP 0 , 2006 .

[83]  P. Donaldson,et al.  Molecular identification of P-glycoprotein: a role in lens circulation? , 2002, Investigative ophthalmology & visual science.

[84]  C. Kushmerick,et al.  The Role of MIP in Lens Fiber Cell Membrane Transport , 1999, The Journal of Membrane Biology.

[85]  R. Mathias.  Epithelial water transport in a balanced gradient system. , 1985, Biophysical journal.

[86]  F. Ismail-Beigi,et al.  Na,K-ATPase in several tissues of the rat: Tissue-specific expression of subunit mRNAs and enzyme activity , 1993, The Journal of Membrane Biology.

[87]  P. Agre,et al.  Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[88]  E. Winterhager.  Gap Junctions in Development and Disease , 2005 .

[89]  L. Ebihara.  Physiology and biophysics of hemi-gap-junctional channels expressed in Xenopus oocytes. , 2003, Acta physiologica Scandinavica.

[90]  Tamir Gonen,et al.  Aquaporin-0 membrane junctions reveal the structure of a closed water pore , 2004, Nature.

[91]  G. McBean,et al.  Molecular mechanisms of cystine transport. , 2001, Biochemical Society transactions.

[92]  M. Tunstall,et al.  Blocking chloride channels in the rat lens: localized changes in tissue hydration support the existence of a circulating chloride flux. , 2000, Investigative ophthalmology & visual science.

[93]  S. Harrison,et al.  Lipid–protein interactions in double-layered two-dimensional AQP0 crystals , 2005 .

[94]  J. Kuszak,et al.  Scanning electron microscopy of the frog lens. , 1982, Experimental eye research.

[95]  J. Rae.  Outwardly rectifying potassium currents in lens epithelial cell membranes. , 1994, Current eye research.

[96]  D. Schubert,et al.  Distribution of the Cystine/Glutamate Antiporter System x− c in the Brain, Kidney, and Duodenum , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[97]  R. Truscott,et al.  An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract. , 1998, Experimental eye research.

[98]  J. Rae,et al.  Sutures of the crystalline lens: a review. , 1984, Scanning electron microscopy.

[99]  D. Goodenough,et al.  Immunolocalization of MP70 in lens fiber 16-17-nm intercellular junctions , 1987, The Journal of cell biology.

[100]  R. Mathias,et al.  Physiological properties of the normal lens. , 1997, Physiological reviews.

[101]  P. Donaldson,et al.  Differential expression of facilitative glucose transporters GLUT1 and GLUT3 in the lens. , 1999, Investigative ophthalmology & visual science.

[102]  O. Candia,et al.  Regional distribution of the Na(+) and K(+) currents around the crystalline lens of rabbit. , 2002, American journal of physiology. Cell physiology.

[103]  P. Donaldson,et al.  Regional differences in cystine accumulation point to a sutural delivery pathway to the lens core. , 2007, Investigative ophthalmology & visual science.

[104]  W. Dean,et al.  Regional distribution of Na,K-ATPase activity in porcine lens epithelium. , 2003, Investigative ophthalmology & visual science.

[105]  C. Paterson,et al.  ATPases and lens ion balance. , 2004, Experimental eye research.

[106]  James E. Hall,et al.  Comparison of the Water Transporting Properties of MIP and AQP1 , 1997, The Journal of Membrane Biology.

[107]  K. Geering.  FXYD proteins: new regulators of Na-K-ATPase. , 2006, American journal of physiology. Renal physiology.

[108]  G. Zampighi,et al.  Single-membrane and cell-to-cell permeability properties of dissociated embryonic chick lens cells , 1992, The Journal of Membrane Biology.

[109]  K. Webb,et al.  Cl- influx into rat cortical lens fiber cells is mediated by a Cl- conductance that is not ClC-2 or -3. , 2004, Investigative ophthalmology & visual science.

[110]  P. Lauf,et al.  K-Cl Cotransport: Properties and Molecular Mechanism , 2001, Cellular Physiology and Biochemistry.

[111]  J. Kuszak,et al.  Lens structure in MIP-deficient mice. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[112]  M. Cynader,et al.  Astrocytes Provide Cysteine to Neurons by Releasing Glutathione , 2000, Journal of neurochemistry.

[113]  D. Murray,et al.  Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens. , 1991, Experimental eye research.