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Inner Blood-Retinal Barrier Regulation in Retinopathies

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1185))

Abstract

The neural retina is protected from the blood circulation by the presence of a highly selective inner blood-retinal barrier (iBRB). The presence of sophisticated tight junctions (TJs) between the endothelial cells (ECs) of the iBRB helps mediate the very low passive permeability of the tissue, permitting entry of nutrients into the retina but excluding harmful toxic material and inflammatory cells. The most highly enriched TJ protein is claudin-5, which is critical in mediating the passive paracellular diffusion barrier properties of the iBRB. In numerous retinal degeneration pathologies, TJ disruption is observed, and a more refined understanding of this disruption could be used for therapeutic benefit.

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References

  • Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53

    Article  CAS  Google Scholar 

  • Arden GB, Sidman RL, Arap W et al (2005) Spare the rod and spoil the eye. Br J Ophthalmol 89:764–769

    Article  CAS  Google Scholar 

  • Argaw AT, Gurfein BT, Zhang Y et al (2009) VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A 106(6):1977–1982

    Article  CAS  Google Scholar 

  • Balda MS, Matter K (2009) Tight junctions and the regulation of gene expression. Biochim Biophys Acta 1788:761–767

    Article  CAS  Google Scholar 

  • Burek M, Arias-Loza PA, Roewer N et al (2010) Claudin-5 as a novel estrogen target in vascular endothelium. Arterioscler Thromb Vasc Biol 30(2):298–304

    Article  CAS  Google Scholar 

  • Campbell M, Nguyen AT, Kiang AS et al (2009) An experimental platform for systemic drug delivery to the retina. Proc Natl Acad Sci U S A 106(42):17817–17822

    Article  CAS  Google Scholar 

  • Campbell M, Nguyen AT, Kiang AS et al (2010) Reversible and size-selective opening of the inner Blood-Retina barrier: a novel therapeutic strategy. Adv Exp Med Biol 664:301–308

    Article  CAS  Google Scholar 

  • Campbell M, Humphries MM, Kiang AS et al (2011) Systemic low-molecular weight drug delivery to pre-selected neuronal regions. EMBO Mol Med 3(4):235–245

    Article  CAS  Google Scholar 

  • Campbell M, Humphries P (2012) The blood-retina barrier: tight junctions and barrier modulation. Adv Exp Med Biol 763:70–84

    Article  CAS  Google Scholar 

  • Daneman R, Rescigno M (2009) The gut immune barrier and the blood-brain barrier: are they so different? Immunity 31:722–735

    Article  CAS  Google Scholar 

  • Daneman R, Zhou L, Kebede AA et al (2010a) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468(7323):562–566

    Article  CAS  Google Scholar 

  • Daneman R, Zhou L, Agalliu D et al (2010b) The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS One 5(10):e13741

    Article  Google Scholar 

  • Díaz-Coránguez M, Ramos C, Antonetti DA (2017) The inner blood-retinal barrier: cellular basis and development. Vis Res 139:123–137

    Article  Google Scholar 

  • Ebnet K (2017) Junctional Adhesion Molecules (JAMs): cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol Rev 97(4):1529–1554

    Article  CAS  Google Scholar 

  • Frank RN, Turczyn TJ, Das A (1990) Pericyte coverage of retinal and cerebral capillaries. Invest Ophthalmol Vis Sci 31:999–1007

    CAS  PubMed  Google Scholar 

  • Furuse M, Hirase T, Itoh M et al (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123(6. Pt 2):1777–1788

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Greene C, Campbell M (2016) Tight junction modulation of the blood brain barrier: CNS delivery of small molecules. Tissue Barriers 4(1):e1138017

    Article  Google Scholar 

  • Hirase T, Staddon JM, Saitou M et al (1997) Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci 110.(Pt 14:1603–1613

    CAS  PubMed  Google Scholar 

  • Ikenouchi J, Sasaki H, Tsukita S et al (2008) Loss of occludin affects tricellular localization of tricellulin. Mol Biol Cell 19(11):4687–4693

    Article  CAS  Google Scholar 

  • Iwamoto N, Higashi T, Furuse M (2014) Localization of angulin-1/LSR and tricellulin at tricellular contacts of brain and retinal endothelial cells in vivo. Cell Struct Funct 39(1):1–8

    Article  CAS  Google Scholar 

  • Keaney J, Campbell M (2015) The dynamic blood-brain barrier. FEBS J 282(21):4067–4079

    Article  CAS  Google Scholar 

  • Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48

    Article  CAS  Google Scholar 

  • Kojima S, Rahner C, Peng S et al (2002) Claudin 5 is transiently expressed during the development of the retinal pigment epithelium. J Membr Biol 186(2):81–88

    Article  CAS  Google Scholar 

  • Koto T, Takubo K, Ishida S et al (2007) Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells. Am J Pathol 170(4):1389–1397

    Article  CAS  Google Scholar 

  • Krause G, Winkler L, Mueller SL et al (2008) Structure and function of claudins. Biochim Biophys Acta 1778:631–645

    Article  CAS  Google Scholar 

  • Liebner S, Fischmann A, Rascher G et al (2000) Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol 100:323–331

    Article  CAS  Google Scholar 

  • Luo Y, Xiao W, Zhu X et al (2011) Differential expression of claudins in retinas during normal development and the angiogenesis of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 52(10):7556–7564

    Article  CAS  Google Scholar 

  • Mineta K, Yamamoto Y, Yamazaki Y et al (2011) Predicted expansion of the claudin multigene family. FEBS Lett 585(4):606–612

    Article  CAS  Google Scholar 

  • Morita K, Sasaki H, Furuse M et al (1999) Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 147:185–194

    Article  CAS  Google Scholar 

  • Nitta T, Hata M, Gotoh S et al (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660

    Article  CAS  Google Scholar 

  • Peppiatt CM, Howarth C, Mobbs P et al (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443(7112):700–704

    Article  CAS  Google Scholar 

  • Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6:193–201

    Article  Google Scholar 

  • Reichenbach A, Bringmann A (2013) New functions of Müller cells. Glia 61(8):651–678

    Article  Google Scholar 

  • Saitou M, Furuse M, Sasaki H et al (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11(12):4131–4142

    Article  CAS  Google Scholar 

  • Taddei A, Giampietro C, Conti A et al (2008) Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol 10(8):923–934

    Article  CAS  Google Scholar 

  • Trost A, Lange S, Schroedl F et al (2016) Brain and retinal pericytes: origin, function and role. Front Cell Neurosci 4(10):20

    Google Scholar 

  • Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293

    Article  CAS  Google Scholar 

  • Vecino E, Rodriguez FD, Ruzafa N et al (2016) Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res 51:1–40

    Article  CAS  Google Scholar 

  • Zihni C, Mills C, Matter K et al (2016) Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol 17(9):564–580

    Article  CAS  Google Scholar 

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Correspondence to Natalie Hudson .

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Hudson, N., Campbell, M. (2019). Inner Blood-Retinal Barrier Regulation in Retinopathies. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_54

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