Skip to main content
SpringerLink
Log in

The Inner Blood-Retinal Barrier

Molecular Structure and Transport Biology

  • Chapter
  • First Online:
Biology and Regulation of Blood-Tissue Barriers

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 763))

Abstract

The inner blood-retinal barrier (inner BRB) is created by complex tight junctions of retinal capillary endothelial cells. Although this barrier prevents the free diffusion of substances between the circulating blood and the neural retina, the inner BRB efficiently supplies nutrients to the retina and removes endobiotics and xenobiotics from the retina to maintain a constant milieu in the neural retina. We review herein the molecular structure and transport mechanism at the inner BRB.

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cunha-Vaz JG. The blood-retinal barriers system. Basic concepts and clinical evaluation. Exp Eye Res 2004; 78:715–721.

    Article  CAS  PubMed  Google Scholar 

  2. Hosoya K, Tomi M. Advances in the cell biology of transport via the inner blood-retinal barrier: establishment of cell lines and transport functions. Biol Pharm Bull 2005; 28:1–8.

    Article  CAS  PubMed  Google Scholar 

  3. Schnaudigel O. Die vitale farbung mit trypanblau an auge. Graefe Arch Ophthal 1913; 86:93–105.

    Article  Google Scholar 

  4. Kim JH, Kim JH, Park JA et al. Blood-neural barrier: intercellular communication at glio-vascular interface. J Biochem Mol Biol 2006; 39:339–345.

    CAS  PubMed  Google Scholar 

  5. Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 1987; 325:253–257.

    Article  CAS  PubMed  Google Scholar 

  6. Janzer RC. The blood-brain barrier: cellular basis. J Inherit Metab Dis 1993; 16:639–647.

    Article  CAS  PubMed  Google Scholar 

  7. Gardner TW, Lieth E, Khin SA et al. Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 1997; 38:2423–2427.

    CAS  PubMed  Google Scholar 

  8. Tout S, Chan-Ling T, Holländer H et al. The role of Müller cells in the formation of the blood-retinal barrier. Neuroscience 1993; 55:291–301.

    Article  CAS  PubMed  Google Scholar 

  9. Abukawa H, Tomi M, Kiyokawa J et al. Modulation of retinal capillary endothelial cells by Müller glial cell-derived factors. Mol Vis 2009; 15:451–457.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. A bbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 2002; 200: 629–638.

    Article  CAS  Google Scholar 

  11. Hori S, Ohtsuki S, Hosoya K et al. A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro. J Neurochem 2004; 89:503–513.

    Article  CAS  PubMed  Google Scholar 

  12. Bandopadhyay R, Orte C, Lawrenson JG et al. Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J Neurocytol 2001; 30:35–44.

    Article  CAS  PubMed  Google Scholar 

  13. Matsugi T, Chen Q, Anderson DR. Contractile responses of cultured bovine retinal pericytes to angiotensin II. Arch Ophthalmol 1997; 115:1281–1285.

    Article  CAS  PubMed  Google Scholar 

  14. Chen Q, Anderson DR. Effect of CO2 on intracellular pH and contraction of retinal capillary pericytes. Invest Ophthalmol Vis Sci 1997; 38:643–651.

    CAS  PubMed  Google Scholar 

  15. Matsugi T, Chen Q, Anderson DR. Adenosine-induced relaxation of cultured bovine retinal pericytes. Invest Ophthalmol Vis Sci 1997; 38:2695–2701.

    CAS  PubMed  Google Scholar 

  16. Hirase T, Staddon JM, Saitou M et al. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci 1997; 110:1603–1613.

    CAS  PubMed  Google Scholar 

  17. Furuse M, Fujita K, Hiiragi T et al. Claudin-1 and-2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1998; 141:1539–1550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bazzoni G, Tonetti P, Manzi L et al. Expression of junctional adhesion molecule-A prevents spontaneous and random motility. J Cell Sci 2005; 118:623–632.

    Article  CAS  PubMed  Google Scholar 

  19. Tomi M, Hosoya K. Application of magnetically isolated rat retinal vascular endothelial cells for the determination of transporter gene expression levels at the inner blood-retinal barrier. J Neurochem 2004; 91:1244–1248.

    Article  CAS  PubMed  Google Scholar 

  20. Tachikawa M, Toki H, Tomi M et al. Gene expression profiles of ATP-binding cassette transporter A and C subfamilies in mouse retinal vascular endothelial cells. Microvasc Res 2008; 75:68–72.

    Article  CAS  PubMed  Google Scholar 

  21. Anderson JM, Fanning AS, Lapierre L et al. Zonula occludens (ZO)-1 and ZO-2: membrane-associated guanylate kinase homologues (MAGuKs) of the tight junction. Biochem Soc Trans 1995; 23:470–475.

    Article  CAS  PubMed  Google Scholar 

  22. Haskins J, Gu L, Wittchen ES et al. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 1998; 141:199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 2004; 84:869–901.

    Article  CAS  PubMed  Google Scholar 

  24. Wolburg H, Noell S, Mack A et al. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res 2009; 335:75–96.

    Article  PubMed  Google Scholar 

  25. Kevil CG, Okayama N, Trocha SD et al. Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: role of occludin in endothelial solute barriers. Microcirculation 1998; 5:197–210.

    Article  CAS  PubMed  Google Scholar 

  26. Antonetti DA, Barber AJ, Khin S et al. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Diabetes 1998; 47:1953–1959.

    Article  CAS  PubMed  Google Scholar 

  27. Yaccino JA, Chang YS, Hollis TM et al. Physiological transport properties of cultured retinal microvascular endothelial cell monolayers. Curr Eye Res 1997; 16:761–768.

    Article  CAS  PubMed  Google Scholar 

  28. Mark KS, Burroughs AR, Brown RC et al. Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature. Am J Physiol Heart Circ Physiol 2004; 286:H174–180.

    Article  CAS  PubMed  Google Scholar 

  29. Kaur C, Sivakumar V, Foulds WS. Early response of neurons and glial cells to hypoxia in the retina. Invest Ophthalmol Vis Sci 2006; 47:1126–1141.

    Article  PubMed  Google Scholar 

  30. Augustin AJ, Breipohl W, Böker T et al. Increased lipid peroxide levels and myeloperoxidase activity in the vitreous of patients suffering from proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 1993; 231:647–650.

    Article  CAS  PubMed  Google Scholar 

  31. Saugstad OD, Rognum TO. High postmortem levels of hypoxanthine in the vitreous humor of premature babies with respiratory distress syndrome. Pediatrics 1988; 81:395–398.

    CAS  PubMed  Google Scholar 

  32. Kaur C, Foulds WS, Ling EA. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Prog Retin Eye Res 2008; 27:622–647.

    Article  CAS  PubMed  Google Scholar 

  33. Niemeyer G. Glucose concentration and retinal function. Clin Neurisci 1997; 4:327–335.

    CAS  Google Scholar 

  34. Tachikawa M, Hosoya K, Ohtsuki S et al. A novel relationship between creatine transport at the blood-brain and blood-retinal barriers, creatine biosynthesis and its use for brain and retinal energy homeostasis. Subcell Biochem 2007; 46:83–98.

    Article  PubMed  Google Scholar 

  35. Hosoya K, Tachikawa M. Inner blood-retinal barrier transporters: role of retinal drug delivery. Pharm Res 2009; 26:2055–2065.

    Article  CAS  PubMed  Google Scholar 

  36. Hosoya K, Tomi M. Inner blood-retinal barrier: transport biology and methodology. In: Ehrhardt C, Kim KJ, eds. Drug Absorption Studies-In Situ, In Vitro and In Silico Models, New York: AAPS Press-Springer, 2008:321–338.

    Chapter  Google Scholar 

  37. Hosoya K, Tomi M, Ohtsuki S et al. Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a transgenic rat. Exp Eye Res 2001; 72:163–172.

    Article  CAS  PubMed  Google Scholar 

  38. Vera JC, Rivas CI, Fischbarg J et al. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature 1993; 364:79–82.

    Article  CAS  PubMed  Google Scholar 

  39. Takata K, Kasahara T, Kasahara M et al. Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat. Invest Ophthalmol Vis Sci 1992; 33:377–383.

    CAS  PubMed  Google Scholar 

  40. Fernandes R, Suzuki K, Kumagai AK. Inner blood-retinal barrier GLUT1 in long-term diabetic rats: an immunogold electron microscopic study. Invest Ophthalmol Vis Sci 2003; 44:3150–3154.

    Article  PubMed  Google Scholar 

  41. Puchowicz MA, Xu K, Magness D et al. Comparison of glucose influx and blood flow in retina and brain of diabetic rats. J Cereb Blood Flow Metab 2004; 24:449–457.

    Article  PubMed  Google Scholar 

  42. Hosoya K, Minamizono A, Katayama K et al. Vitamin C transport in oxidized form across the rat blood-retinal barrier. Invest Ophthalmol Vis Sci 2004; 45:1232–1239.

    Article  PubMed  Google Scholar 

  43. Hosoya K, Nakamura G, Akanuma S et al. Dehydroascorbic acid uptake and intracellular ascorbic acid accumulation in cultured Müller glial cells (TR-MUL). Neurochem Int 2008; 52:1351–1357.

    Article  CAS  PubMed  Google Scholar 

  44. Ennis SR, Johnson JE, Pautler EL. In situ kinetics of glucose transport across the blood-retinal barrier in normal rats and rats with streptozocin-induced diabetes. Invest Ophthalmol Vis Sci 1982; 23:447–456.

    CAS  PubMed  Google Scholar 

  45. Minamizono A, Tomi M, Hosoya K. Inhibition of dehydroascorbic acid transport across the rat blood-retinal and-brain barriers in experimental diabetes. Biol Pharm Bull 2006; 29:2148–2150.

    Article  CAS  PubMed  Google Scholar 

  46. Nagase K, Tomi M, Tachikawa M et al. Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. Biochim Biophys Acta 2006; 1758:13–19.

    Article  CAS  PubMed  Google Scholar 

  47. Baldwin SA, Beal PR, Yao SY et al. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 2004; 447:735–743.

    Article  CAS  PubMed  Google Scholar 

  48. Yao SY, Ng AM, Sundaram M et al. Transport of antiviral 3’-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol 2001; 18:161–167.

    Article  CAS  PubMed  Google Scholar 

  49. Tomi M, Kitade N, Hirose S et al. Cationic amino acid transporter 1-mediated L-arginine transport at the inner blood-retinal barrier. J Neurochem 2009; 111:716–725.

    Article  CAS  PubMed  Google Scholar 

  50. Törnquist P, Alm A. Carrier-mediated transport of amino acids through the blood-retinal and the blood-brain barriers. Graefes Arch Clin Exp Ophthalmol 1986; 224:21–25.

    Article  PubMed  Google Scholar 

  51. Lin CT, Song GX, Wu JY. Ultrastructural demonstration of L-glutamate decarboxylase and cysteinesulfinic acid decarboxylase in rat retina by immunocytochemistry. Brain Res 1985; 331:71–80.

    Article  CAS  PubMed  Google Scholar 

  52. Tomi M, Terayama T, Isobe T et al. Function and regulation of taurine transport at the inner blood-retinal barrier. Microvasc Res 2007; 73:100–106.

    Article  CAS  PubMed  Google Scholar 

  53. Tomi M, Tajima A, Tachikawa M et al. Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta 2008; 1778:2138–2142.

    Article  CAS  PubMed  Google Scholar 

  54. Tomi M, Mori M, Tachikawa M et al. L-type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier. Invest Ophthalmol Vis Sci 2005; 46:2522–2530.

    Article  PubMed  Google Scholar 

  55. Kageyama T, Nakamura M, Matsuo A et al. The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res 2000; 879:115–121.

    Article  CAS  PubMed  Google Scholar 

  56. Bodis-Wollner I. Visual electrophysiology in Parkinson’s disease: PERG, VEP and visual P300. Clin Electroencephalogr 1997; 28:143–147.

    Article  CAS  PubMed  Google Scholar 

  57. Bhaskar PA, Vanchilingam S, Bhaskar EA et al. Effect of L-dopa on visual evoked potential in patients with Parkinson’s disease. Neurology 1986; 36:1119–1121.

    Article  CAS  PubMed  Google Scholar 

  58. Hosoya K, Kyoko H, Toyooka N et al. Evaluation of amino acid-mustard transport as L-type amino acid transporter 1 (LAT1)-mediated alkylating agents. Biol Pharm Bull 2008; 31:2126–2130.

    Article  CAS  PubMed  Google Scholar 

  59. Tomi M, Hosoya K, Takanaga H et al. Induction of xCT gene expression and L-cystine transport activity by diethyl maleate at the inner blood-retinal barrier. Invest Ophthalmol Vis Sci 2002; 43:774–779.

    PubMed  Google Scholar 

  60. Hosoya K, Saeki S, Terasaki T. Activation of carrier-mediated transport of L-cystine at the blood-brain and blood-retinal barriers in vivo. Microvasc Res 2001; 62:136–142.

    Article  CAS  PubMed  Google Scholar 

  61. Okamoto M, Akanuma S, Tachikawa M et al. Characteristics of glycine transport across the inner blood-retinal barrier. Neurochem Int 2009; 55:789–795.

    Article  CAS  PubMed  Google Scholar 

  62. Tachikawa M, Takeda Y, Tomi M et al. Involvement of OCTN2 in the transport of acetyl-L-carnitine across the inner blood-retinal barrier. Invest Ophthalmol Vis Sci 2010; 51:430–436.

    Article  PubMed  Google Scholar 

  63. Nakashima T, Tomi M, Katayama K et al. Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier. J Neurochem 2004; 89:1454–1461.

    Article  CAS  PubMed  Google Scholar 

  64. Nakashima T, Tomi M, Tachikawa M et al. Evidence for creatine biosynthesis in Müller glia. Glia 2005; 52:47–52.

    Article  PubMed  Google Scholar 

  65. Hosoya K, Ichikawa T, Akanuma S et al. Glycine and L-arginine transport in cultured Müller glial cells (TR-MUL). Neurochem Int 2010; 57:262–268.

    Article  CAS  PubMed  Google Scholar 

  66. Arunchaipong K, Sattayasai N, Sattayasai J et al. A biotin-coupled bifunctional enzyme exhibiting both glutamine synthetase activity and glutamate decarboxylase activity. Curr Eye Res 2009; 34:809–818.

    Article  CAS  PubMed  Google Scholar 

  67. Ohkura Y, Akanuma SI, Tachikawa M et al. Blood-to-retina transport of biotin via Na(+)-dependent multivitamin transporter (SMVT) at the inner blood-retinal barrier. Exp Eye Res 2010; 91:387–392.

    Article  CAS  PubMed  Google Scholar 

  68. Tomi M, Arai K, Tachikawa M et al. Na(+)-independent choline transport in rat retinal capillary endothelial cells. Neurochem Res 2007; 32:1833–1842.

    Article  CAS  PubMed  Google Scholar 

  69. Karlsson C, Mäepea O, Alm A. Choline transport through the blood-retinal and the blood-brain barrier in vivo. Acta Ophthalmol (Copenh) 1984; 62:763–766.

    Article  CAS  Google Scholar 

  70. Hosoya K, Fujita K, Tachikawa M. Involvement of reduced folate carrier 1 in the inner blood-retinal barrier transport of methyltetrahydrofolate. Drug Metab Pharmacokinet 2008; 23:285–292.

    Article  CAS  PubMed  Google Scholar 

  71. Alm A, Törnquist P. Lactate transport through the blood-retinal and the blood-brain barrier in rats. Ophthalmic Res 1985; 17:181–184.

    Article  CAS  PubMed  Google Scholar 

  72. Gerhart DZ, Leino RL, Drewes LR. Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina. Neuroscience 1999; 92:367–375.

    Article  CAS  PubMed  Google Scholar 

  73. Hosoya K, Kondo T, Tomi M et al. MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. Pharm Res 2001;18:1669–1676.

    Article  CAS  PubMed  Google Scholar 

  74. Tachikawa M, Okayasu S, Hosoya K. Functional involvement of scavenger receptor class B, type I, in the uptake of alpha-tocopherol using cultured rat retinal capillary endothelial cells. Mol Vis 2007; 13:2041–2047.

    CAS  PubMed  Google Scholar 

  75. Heacock AM, Dodd MS, Fisher SK. Regulation of volume-sensitive osmolyte efflux from human SH-SY5Y neuroblastoma cells following activation of lysophospholipid receptors. J Pharmacol Exp Ther 2006; 317:685–693.

    Article  CAS  PubMed  Google Scholar 

  76. Fisher SK, Cheema TA, Foster DJ. Volume-dependent osmolyte efflux from neural tissues: regulation by G-protein-coupled receptors. J Neurochem 2008; 106:1998–2014.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. McManus ML, Churchwell KB, Strange K. Regulation of cell volume in health and disease. N Engl J Med 1995; 333:1260–1266.

    Article  CAS  PubMed  Google Scholar 

  78. Pow DV, Sullivan R, Reye P et al. Localization of taurine transporters, taurine and 3H taurine accumulation in the rat retina, pituitary and brain. Glia 2002; 37:153–168.

    Article  PubMed  Google Scholar 

  79. Tachikawa M, Tsuji K, Ikeda S et al. Lysophospholipids enhance taurine release from rat retinal vascular endothelial cells under hypoosmotic stress. Microvasc Res 2009; 78:332–337.

    Article  CAS  PubMed  Google Scholar 

  80. Nakakariya M, Shimada T, Irokawa M et al. Predominant contribution of rat organic anion transporting polypeptide-2 (Oatp2) to hepatic uptake of beta-lactam antibiotics. Pharm Res 2008; 25:578–585.

    Article  CAS  PubMed  Google Scholar 

  81. Katayama K, Ohshima Y, Tomi M et al. Application of microdialysis to evaluate the efflux transport of estradiol 17-beta glucuronide across the rat blood-retinal barrier. J Neurosci Methods 2006; 156:249–256.

    Article  CAS  PubMed  Google Scholar 

  82. Noé B, Hagenbuch B, Stieger B et al. Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proc Natl Acad Sci USA 1994; 94:10346–10350.

    Article  Google Scholar 

  83. Gao B, Wenzel A, Grimm C et al. Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Invest Ophthalmol Vis Sci 2002; 43:510–514.

    PubMed  Google Scholar 

  84. Sugiyama D, Kusuhara H, Shitara Y et al. Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther 2001; 298:316–322.

    CAS  PubMed  Google Scholar 

  85. Kikuchi R, Kusuhara H, Sugiyama Da et al. Contribution of organic anion transporter 3 (Slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood-brain barrier. J Pharmacol Exp Ther 2003; 306:51–58.

    Article  CAS  PubMed  Google Scholar 

  86. Somervaille TC, Hann IM, Harrison G et al. MRC Childhood Leukaemia Working Party. Intraocular relapse of childhood acute lymphoblastic leukaemia. Br J Haematol 2003; 121:280–288.

    Article  PubMed  Google Scholar 

  87. Betz AL, Goldstein GW. Transport of hexoses, potassium and neutral amino acids into capillaries isolated from bovine retina. Exp Eye Res 1980; 30:593–605.

    Article  CAS  PubMed  Google Scholar 

  88. Hosoya K, Makihara A, Tsujikawa Y et al. Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin and 6-mercaptopurine. J Pharmacol Exp Ther 2009; 329:87–93.

    Article  CAS  PubMed  Google Scholar 

  89. Yoneyama D, Shinozaki Y, Lu WL et al. Involvement of system A in the retina-to-blood transport of L-proline across the inner blood-retinal barrier. Exp Eye Res 2010; 90:507–513.

    Article  CAS  PubMed  Google Scholar 

  90. LaNoue KF, Berkich DA, Conway M et al. Role of specific aminotransferases in de novo glutamate synthesis and redox shuttling in the retina. J Neurosci Res 2001; 66:914–922.

    Article  CAS  PubMed  Google Scholar 

  91. Levkovitch-Verbin H, Martin KR, Quigley HA et al. Measurement of amino acid levels in the vitreous humor of rats after chronic intraocular pressure elevation or optic nerve transection. J Glaucoma 2002; 11:396–405.

    Article  PubMed  Google Scholar 

  92. Maines LW, Antonetti DA, Wolpert EB et al. Evaluation of the role of P-glycoprotein in the uptake of paroxetine, clozapine, phenytoin and carbamazapine by bovine retinal endothelial cells. Neuropharmacology 2005; 49:610–617.

    Article  CAS  PubMed  Google Scholar 

  93. Shen J, Cross ST, Tang-Liu DD et al. Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier. Pharm Res 2003; 20:1357–1363.

    Article  CAS  PubMed  Google Scholar 

  94. BenEzra D, Maftzir G. Ocular penetration of cyclosporin A. The rabbit eye. Invest Ophthalmol Vis Sci 1990; 31:1362–1366.

    CAS  PubMed  Google Scholar 

  95. BenEzra D, Maftzir G. Ocular penetration of cyclosporine A in the rat eye. Arch Ophthalmol 1990; 108:584–587.

    Article  CAS  PubMed  Google Scholar 

  96. BenEzra D, Maftzir G, de Courten C et al. Ocular penetration of cyclosporin A. III: The human eye. Br J Ophthalmol 1990; 74:350–352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Choudhuri S. Klaassen CD. Structure, function, expression, genomic organization and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP) and ABCG2 (BCRP) efflux transporters. Int J Toxicol 2006; 25:231–259.

    Article  CAS  PubMed  Google Scholar 

  98. Tagami M, Kusuhara S, Honda S et al. Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy. Brain Res 2009; 1283:186–193.

    Article  CAS  PubMed  Google Scholar 

  99. Smeets PH, van Aubel RA, Wouterse AC et al. Contribution of multidrug resistance protein 2 (MRP2/ ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 2004; 15:2828–2835.

    Article  CAS  PubMed  Google Scholar 

  100. Uchida Y, Kamiie J, Ohtsuki S et al. Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res 2007; 24:2281–2296.

    Article  CAS  PubMed  Google Scholar 

  101. Asashima T, Hori S, Ohtsuki S et al. ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells. Pharm Res 2006; 23:1235–1242.

    Article  CAS  PubMed  Google Scholar 

  102. Boulton M, Rozanowska M, Rozanowski B. Retinal photodamage. J Photochem Photobiol B 2001; 64:144–161.

    Article  CAS  PubMed  Google Scholar 

  103. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001; 42:1007–1017.

    CAS  PubMed  Google Scholar 

  104. Tomi M, Hosoya K. The role of blood-ocular barrier transporters in retinal drug disposition: an overview. Expert Opin Drug Metab Toxicol 2010; 6:1111–1124.

    Article  CAS  PubMed  Google Scholar 

  105. Kamiie J, Ohtsuki S, Iwase R et al. Quantitative atlas of membrane transporter proteins: development and application of a highly sensitive simultaneous LC/MS/MS method combined with novel in-silico peptide selection criteria. Pharm Res 2008; 25:1469–1483.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan

    Ken-ichi Hosoya & Masanori Tachikawa

Authors
  1. Ken-ichi Hosoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masanori Tachikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ken-ichi Hosoya .

Editor information

Editors and Affiliations

  1. Center for Biomedical Research, Population Council, New York, New York, USA

    C. Yan Cheng PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Hosoya, Ki., Tachikawa, M. (2013). The Inner Blood-Retinal Barrier. In: Cheng, C.Y. (eds) Biology and Regulation of Blood-Tissue Barriers. Advances in Experimental Medicine and Biology, vol 763. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4711-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation