Skip to main content
SpringerLink
Log in

Vitamin C Transport, Delivery, and Function in the Anterior Segment of the Eye

  • Chapter
Ocular Transporters In Ophthalmic Diseases And Drug Delivery

Part of the book series: Ophthalmology Research ((OPHRES))

  • 1023 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 1. Taylor A, Jacques PF, Nadler D, Morrow F, Sulsky SI, Shepard D. Relationship in humans between ascorbic acid consumption and levels of total and reduced ascorbic acid in lens, aqueous humor, and plasma. Curr Eye Res 1991;10(8):751–759.

    Article  PubMed  CAS  Google Scholar 

  2. 2. McGahan MC. Ascorbic acid levels in aqueous and vitreous humors of the rabbit: effects of inflammation and ceruloplasmin. Exp Eye Res 1985;41(3):291–298.

    Article  PubMed  CAS  Google Scholar 

  3. 3. Delamere NA. Ascorbic acid and the eye. Subcell Biochem 1996;25:313–329.

    PubMed  CAS  Google Scholar 

  4. 4. Rose RC, Bode AM. Ocular ascorbate transport and metabolism. Comp Biochem Physiol A 1991;100(2):273–285.

    Article  PubMed  CAS  Google Scholar 

  5. 5. Packer L, Fuchs J. Vitamin C in health and disease. New York: M. Dekker; 1997.

    Google Scholar 

  6. 6. Levine M, Morita K. Ascorbic acid in endocrine systems. Vitam Horm 1985;42:1–64.

    Article  PubMed  CAS  Google Scholar 

  7. 7. Reiss GR, Werness PG, Zollman PE, Brubaker RF. Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals. Arch Ophthalmol 1986;104(5):753v755.

    Google Scholar 

  8. 8. Reddy VN, Giblin FJ, Lin LR, Chakrapani B. The effect of aqueous humor ascorbate on ultraviolet-B-induced DNA damage in lens epithelium. Invest Ophthalmol Vis Sci 1998;39(2):344–350.

    PubMed  CAS  Google Scholar 

  9. 9. Mackic JB, Ross-Cisneros FN, McComb JG et al. Galactose-induced cataract formation in guinea pigs: morphologic changes and accumulation of galactitol. Invest Ophthalmol Vis Sci 1994;35(3):804–810.

    PubMed  CAS  Google Scholar 

  10. 10. Wolff SP, Wang GM, Spector A. Pro-oxidant activation of ocular reductants. 1. Copper and riboflavin stimulate ascorbate oxidation causing lens epithelial cytotoxicity in vitro. Exp Eye Res 1987;45(6):777–789.

    Article  PubMed  CAS  Google Scholar 

  11. 11. Giblin FJ, McCready JP, Kodama T, Reddy VN. A direct correlation between the levels of ascorbic acid and H2O2 in aqueous humor. Exp Eye Res 1984;38(1):87–93.

    Article  PubMed  CAS  Google Scholar 

  12. 12. Sasaki K. Cataract classification systems in epidemiological studies. Dev Ophthalmol 1991;21:97–102.

    Article  PubMed  CAS  Google Scholar 

  13. 13. Spector A. Oxidative stress-induced cataract: mechanism of action. FASEB J 1995;9(12): 1173–1182.

    PubMed  CAS  Google Scholar 

  14. 14. Welch RW, Wang Y, Crossman A, Jr., Park JB, Kirk KL, Levine M. Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms. J Biol Chem 1995;270(21):12584–12592.

    Article  PubMed  CAS  Google Scholar 

  15. 15. Dyer DL, Kanai Y, Hediger MA, Rubin SA, Said HM. Expression of a rabbit renal ascorbic acid transporter in Xenopus laevis oocytes. Am J Physiol 1994;267(1 Pt 1):C301–C306.

    PubMed  CAS  Google Scholar 

  16. 16. Vera JC, Rivas CI, Fischbarg J, Golde DW. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 1993;364(6432):79–82.

    Article  PubMed  CAS  Google Scholar 

  17. 17. Corti A, Ferrari SM, Lazzarotti A et al. UV light increases vitamin C uptake by bovine lens epithelial cells. Mol Vis 2004;10:533–536.

    PubMed  CAS  Google Scholar 

  18. 18. Hughes RE, Hurley RJ. In vitro uptake of ascorbic acid by the guinea pig eye lens. Exp Eye Res 1970;9(2):175–180.

    Article  PubMed  CAS  Google Scholar 

  19. 19. Kern HL, Zolot SL. Transport of vitamin C in the lens. Curr Eye Res 1987;6(7):885–896.

    Article  PubMed  CAS  Google Scholar 

  20. 20. DiMattio J. Active transport of ascorbic acid into lens epithelium of the rat. Exp Eye Res 1989;49(5):873–885.

    Article  PubMed  CAS  Google Scholar 

  21. 21. DiMattio J. A comparative study of ascorbic acid entry into aqueous and vitreous humors of the rat and guinea pig. Invest Ophthalmol Vis Sci 1989;30(11):2320–2331.

    PubMed  CAS  Google Scholar 

  22. 22. Daruwala R, Song J, Koh WS, Rumsey SC, Levine M. Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett 1999;460(3):480–484.

    Article  PubMed  CAS  Google Scholar 

  23. 23. Rajan DP, Huang W, Dutta B et al. Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function. Biochem Biophys Res Commun 1999;262(3):762–768.

    Article  PubMed  CAS  Google Scholar 

  24. 24. Tsukaguchi H, Tokui T, Mackenzie B et al. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 1999;399(6731):70–75.

    Article  PubMed  CAS  Google Scholar 

  25. 25. Wang H, Dutta B, Huang W et al. Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim Biophys Acta 1999;1461(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  26. 26. Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton CC, Hediger MA. Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem Biophys Res Commun 2000;267(2):488–494.

    Article  PubMed  CAS  Google Scholar 

  27. 27. Eck P, Erichsen HC, Taylor JG et al. Comparison of the genomic structure and variation in the two human sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2. Hum Genet 2004;115(4):285–294.

    Article  PubMed  CAS  Google Scholar 

  28. 28. Wilson JX. Regulation of vitamin C transport. Annu Rev Nutr 2005;25:105–125.

    Article  PubMed  CAS  Google Scholar 

  29. 29. Korcok J, Dixon SJ, Lo TC, Wilson JX. Differential effects of glucose on dehydroascorbic acid transport and intracellular ascorbate accumulation in astrocytes and skeletal myocytes. Brain Res 2003;993(1–2):201–207.

    Article  PubMed  CAS  Google Scholar 

  30. 30. Sotiriou S, Gispert S, Cheng J et al. Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 2002;8(5):514–517.

    Article  PubMed  CAS  Google Scholar 

  31. 31. Kuo SM, MacLean ME, McCormick K, Wilson JX. Gender and sodium-ascorbate transporter isoforms determine ascorbate concentrations in mice. J Nutr 2004;134(9):2216–2221.

    PubMed  CAS  Google Scholar 

  32. 32. Liang WJ, Johnson D, Ma LS, Jarvis SM, Wei-Jun L. Regulation of the human vitamin C transporters expressed in COS-1 cells by protein kinase C [corrected]. Am J Physiol Cell Physiol 2002;283(6):C1696–C1704.

    PubMed  CAS  Google Scholar 

  33. 33. Michels AJ, Joisher N, Hagen TM. Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Arch Biochem Biophys 2003;410(1):112–120.

    Article  PubMed  CAS  Google Scholar 

  34. 34. Kannan R, Stolz A, Ji Q, Prasad PD, Ganapathy V. Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT2. Exp Eye Res 2001;73(2): 159–165.

    Article  PubMed  CAS  Google Scholar 

  35. 35. Obrenovich ME, Fan X, Satake M et al. Relative suppression of the sodium-dependent Vitamin C transport in mouse versus human lens epithelial cells. Mol Cell Biochem 2006;293:53–62.

    Article  PubMed  CAS  Google Scholar 

  36. 36. Mody VC, Jr., Kakar M, Elfving A, Soderberg PG, Lofgren S. Ascorbate in the guinea pig lens: dependence on drinking water supplementation. Acta Ophthalmol Scand 2005;83(2):228–233.

    Article  PubMed  CAS  Google Scholar 

  37. 37. Lutsenko EA, Carcamo JM, Golde DW. A human sodium-dependent vitamin C transporter 2 isoform acts as a dominant-negative inhibitor of ascorbic acid transport. Mol Cell Biol 2004;24(8):3150–3156.

    Article  PubMed  CAS  Google Scholar 

  38. 38. Pirie A, Wood C. Effects of vitamin A deficiency in the rabbit: 1. On vitamin C metabolism. 2. On power to use preformed vitamin A. Biochem J 1946;40(4):557–560.

    CAS  Google Scholar 

  39. 39. Reim M, Luthe P. Compartmentation of redox metabolites in the anterior eye segment? Albrecht Von Graefes Arch Klin Exp Ophthalmol 1977;204(2):135–140.

    Article  PubMed  CAS  Google Scholar 

  40. 40. Ringvold A, Anderssen E, Kjonniksen I. Distribution of ascorbate in the anterior bovine eye. Invest Ophthalmol Vis Sci 2000;41(1):20–23.

    PubMed  CAS  Google Scholar 

  41. 41. Paterson CA, O'Rourke MC. Vitamin C levels in human tears. Arch Ophthalmol 1987;105(3):376–377.

    PubMed  CAS  Google Scholar 

  42. 42. Schell DA, Bode AM. Measurement of ascorbic acid and dehydroascorbic acid in mammalian tissue utilizing HPLC and electrochemical detection. Biomed Chromatogr 1993;7(5): 267–272.

    Article  PubMed  CAS  Google Scholar 

  43. 43. Varma SD, Chand D, Sharma YR, Kuck JF, Jr., Richards RD. Oxidative stress on lens and cataract formation: role of light and oxygen. Curr Eye Res 1984;3(1):35–57.

    Article  PubMed  CAS  Google Scholar 

  44. 44. Levene CI, Bates CJ. Ascorbic acid and collagen synthesis in cultured fibroblasts. Ann NY Acad Sci 1975;258:288–306.

    Article  PubMed  CAS  Google Scholar 

  45. 45. Murad S, Tajima S, Johnson GR, Sivarajah S, Pinnell SR. Collagen synthesis in cultured human skin fibroblasts: effect of ascorbic acid and its analogs. J Invest Dermatol 1983;81(2):158–162.

    Article  PubMed  CAS  Google Scholar 

  46. 46. Saika S, Kanagawa R, Uenoyama K, Hiroi K, Hiraoka J. L-ascorbic acid 2-phosphate, a phosphate derivative of L-ascorbic acid, enhances the growth of cultured rabbit keratocytes. Graefes Arch Clin Exp Ophthalmol 1991;229(1):79–83.

    Article  PubMed  CAS  Google Scholar 

  47. 47. Saika S, Uenoyama K, Hiroi K, Ooshima A. L-ascorbic acid 2-phosphate enhances the production of type I and type III collagen peptides in cultured rabbit keratocytes. Ophthalmic Res 1992;24(2):68–72.

    Article  PubMed  CAS  Google Scholar 

  48. 48. Pfister RR, Paterson CA. Ascorbic acid in the treatment of alkali burns of the eye. Ophthalmology 1980;87(10):1050–1057.

    PubMed  CAS  Google Scholar 

  49. 49. Pfister RR, Hayes SA, Paterson CA. The influence of parenteral ascorbate on the strength of corneal wounds. Invest Ophthalmol Vis Sci 1981;21(1 Pt 1):80–86.

    PubMed  CAS  Google Scholar 

  50. 50. Williams RN, Paterson CA. Modulation of corneal lipoxygenase by ascorbic acid. Exp Eye Res 1986;43(1):7–13.

    Article  PubMed  CAS  Google Scholar 

  51. 51. Williams RN, Paterson CA. A protective role for ascorbic acid during inflammatory episodes in the eye. Exp Eye Res 1986;42(3):211–218.

    Article  PubMed  CAS  Google Scholar 

  52. 52. Candia OA, Askew WA. Active sodium transport in the isolated bullfrog cornea. Biochim Biophys Acta 1968;163(2):262–265.

    Article  PubMed  CAS  Google Scholar 

  53. 53. Klyce SD. Transport of Na, Cl, and water by the rabbit corneal epithelium at resting potential. Am J Physiol 1975;228(5):1446–1452.

    PubMed  CAS  Google Scholar 

  54. 54. Klyce SD, Wong RK. Site and mode of adrenaline action on chloride transport across the rabbit corneal epithelium. J Physiol 1977;266(3):777–799.

    PubMed  CAS  Google Scholar 

  55. 55. Zadunaisky JA. Active transport of chloride across the cornea. Nature 1966;209(5028): 1136–1137.

    Article  PubMed  CAS  Google Scholar 

  56. 56. McGahan MC, Bentley PJ. Stimulation of transepithelial sodium and chloride transport by ascorbic acid. Induction of Na+ channels is inhibited by amiloride. Biochim Biophys Acta 1982;689(2):385–392.

    Article  PubMed  CAS  Google Scholar 

  57. 57. Scott WN, Cooperstein DF. Ascorbic acid stimulates chloride transport in the amphibian cornea. Invest Ophthalmol 1975;14(10):763–766.

    PubMed  CAS  Google Scholar 

  58. 58. Reid B, Song B, McCaig CD, Zhao M. Wound healing in rat cornea: the role of electric currents. FASEB J 2005;19(3):379–386.

    Article  PubMed  CAS  Google Scholar 

  59. 59. DiMattio J. Ascorbic acid entry into cornea of rat and guinea pig. Cornea 1992;11(1):53–65.

    Article  PubMed  CAS  Google Scholar 

  60. 60. DiMattio J. Decreased ascorbic acid entry into cornea of streptozotocin-diabetic rats and guinea-pigs. Exp Eye Res 1992;55(2):337–344.

    Article  PubMed  CAS  Google Scholar 

  61. 61. Bode AM, Vanderpool SS, Carlson EC, Meyer DA, Rose RC. Ascorbic acid uptake and metabolism by corneal endothelium. Invest Ophthalmol Vis Sci 1991;32(8):2266–2271.

    PubMed  CAS  Google Scholar 

  62. 62. Talluri RS, Katragadda S, Pal D, Mitra AK. Mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells: evidence for the involvement of sodium-dependent vitamin C transporter 2. Curr Eye Res 2006;31(6):481–489.

    Article  PubMed  CAS  Google Scholar 

  63. 63. Dreyer R, Rose RC. Lacrimal gland uptake and metabolism of ascorbic acid. Proc Soc Exp Biol Med 1993;202(2):212–216.

    PubMed  CAS  Google Scholar 

  64. 64. Srinivasan BD, Jakobiec FA, Iwamoto T. Conjunctiva. In: Jakobiec F.A., editor. Ocular Anatomy, Embryology, and Teratology. Philadelphia: Harper and Row; 1982. p. 733–760.

    Google Scholar 

  65. 65. Shiue MH, Kulkarni AA, Gukasyan HJ, Swisher JB, Kim KJ, Lee VH. Pharmacological modulation of fluid secretion in the pigmented rabbit conjunctiva. Life Sci 2000;66(7):L105–L111.

    Article  Google Scholar 

  66. 66. Hosoya K, Kompella UB, Kim KJ, Lee VH. Contribution of Na(+)-glucose cotransport to the short-circuit current in the pigmented rabbit conjunctiva. Curr Eye Res 1996;15(4):447–451.

    Article  PubMed  CAS  Google Scholar 

  67. 67. Shi XP, Candia OA. Active sodium and chloride transport across the isolated rabbit conjunctiva. Curr Eye Res 1995;14(10):927–935.

    Article  PubMed  CAS  Google Scholar 

  68. 68. Kompella UB, Kim KJ, Shiue MH, Lee VH. Possible existence of Na(+)-coupled amino acid transport in the pigmented rabbit conjunctiva. Life Sci 1995;57(15):1427–1431.

    Article  PubMed  CAS  Google Scholar 

  69. 69. Hosoya K, Horibe Y, Kim KJ, Lee VH. Nucleoside transport mechanisms in the pigmented rabbit conjunctiva. Invest Ophthalmol Vis Sci 1998;39(2):372–377.

    PubMed  CAS  Google Scholar 

  70. 70. Kompella UB, Kim KJ, Lee VH. Active chloride transport in the pigmented rabbit conjunctiva. Curr Eye Res 1993;12(12):1041–1048.

    Article  PubMed  CAS  Google Scholar 

  71. 71. Horibe Y, Hosoya K, Kim KJ, Ogiso T, Lee VH. Polar solute transport across the pigmented rabbit conjunctiva: size dependence and the influence of 8-bromo cyclic adenosine monophosphate. Pharm Res 1997;14(9):1246–1251.

    Article  PubMed  CAS  Google Scholar 

  72. 72. Hosoya K, Lee VH. Cidofovir transport in the pigmented rabbit conjunctiva. Curr Eye Res 1997;16(7):693–697.

    Article  PubMed  CAS  Google Scholar 

  73. 73. Saha P, Uchiyama T, Kim KJ, Lee VH. Permeability characteristics of primary cultured rabbit conjunctival epithelial cells to low molecular weight drugs. Curr Eye Res 1996;15(12): 1170–1174.

    Article  PubMed  CAS  Google Scholar 

  74. 74. Rose RC, Richer SP, Bode AM. Ocular oxidants and antioxidant protection. Proc Soc Exp Biol Med 1998; 217(4):397–407.

    PubMed  CAS  Google Scholar 

  75. 75. Gogia R, Richer SP, Rose RC. Tear fluid content of electrochemically active components including water soluble antioxidants. Curr Eye Res 1998;17(3):257–263.

    Article  PubMed  CAS  Google Scholar 

  76. 76. Batey DW, Eckhert CD. Analysis of flavins in ocular tissues of the rabbit. Invest Ophthalmol Vis Sci 1991;32(7):1981–1985.

    PubMed  CAS  Google Scholar 

  77. 77. Gukasyan HJ, Lee VH, Kim KJ, Kannan R. Net glutathione secretion across primary cultured rabbit conjunctival epithelial cell layers. Invest Ophthalmol Vis Sci 2002;43(4):1154–1161.

    PubMed  Google Scholar 

  78. 78. Kuizenga A, van Haeringen NJ, Kijlstra A. Inhibition of hydroxyl radical formation by human tears. Invest Ophthalmol Vis Sci 1987;28(2):305–313.

    PubMed  CAS  Google Scholar 

  79. 79. Crouch RK, Goletz P, Snyder A, Coles WH. Antioxidant enzymes in human tears. J Ocul Pharmacol 1991;7(3):253–258.

    PubMed  CAS  Google Scholar 

  80. 80. Patel S, Plaskow J, Ferrier C. The influence of vitamins and trace element supplements on the stability of the pre-corneal tear film. Acta Ophthalmol (Copenh) 1993;71(6):825–829.

    Article  CAS  Google Scholar 

  81. 81. Peponis V, Papathanasiou M, Kapranou A et al. Protective role of oral antioxidant supplementation in ocular surface of diabetic patients. Br J Ophthalmol 2002;86(12):1369–1373.

    Article  PubMed  CAS  Google Scholar 

  82. 82. Peponis V, Bonovas S, Kapranou A et al. Conjunctival and tear film changes after vitamin C and E administration in non-insulin dependent diabetes mellitus. Med Sci Monit 2004;10(5):CR213–CR217.

    PubMed  CAS  Google Scholar 

  83. 83. Freyschuss A, Xiu RJ, Zhang J et al. Vitamin C reduces cholesterol-induced microcirculatory changes in rabbits. Arterioscler Thromb Vasc Biol 1997;17(6):1178–1184.

    PubMed  CAS  Google Scholar 

  84. 84. Amemiya T. The eye and nutrition. Jpn J Ophthalmol 2000;44(3):320.

    Article  PubMed  Google Scholar 

  85. 85. Tseng SC, Hirst LW, Maumenee AE, Kenyon KR, Sun TT, Green WR. Possible mechanisms for the loss of goblet cells in mucin-deficient disorders. Ophthalmology 1984;91(6):545–552.

    PubMed  CAS  Google Scholar 

  86. 86. Choy CK, Benzie IF, Cho P. Ascorbic acid concentration and total antioxidant activity of human tear fluid measured using the FRASC assay. Invest Ophthalmol Vis Sci 2000;41(11):3293–3298.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Doheny Eye Institute, University Of Southern California, Doheny Vision Research Center, Los Angeles, CA, USA

    Ram Kannan

  2. Pfizer Global Research and Development, Pfizer Inc. La Jolla Laboratories, San Diego, CA, USA

    Hovhannes J. Gukasyan

Authors
  1. Ram Kannan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hovhannes J. Gukasyan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA

    Joyce Tombran-Tink Phd  & Joyce Tombran-Tink Phd  & 

  2. Department of Neural andBehavioral Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA

    Colin J. Barnstable Dphil  & Colin J. Barnstable Dphil  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science + Business Media, LLC

About this chapter

Cite this chapter

Kannan, R., Gukasyan, H.J. (2008). Vitamin C Transport, Delivery, and Function in the Anterior Segment of the Eye. In: Tombran-Tink, J., Barnstable, C.J. (eds) Ocular Transporters In Ophthalmic Diseases And Drug Delivery. Ophthalmology Research. Humana Press. https://doi.org/10.1007/978-1-59745-375-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-375-2_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-958-1

  • Online ISBN: 978-1-59745-375-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation