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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53
Arden GB, Sidman RL, Arap W et al (2005) Spare the rod and spoil the eye. Br J Ophthalmol 89:764–769
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
Balda MS, Matter K (2009) Tight junctions and the regulation of gene expression. Biochim Biophys Acta 1788:761–767
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
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
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
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
Campbell M, Humphries P (2012) The blood-retina barrier: tight junctions and barrier modulation. Adv Exp Med Biol 763:70–84
Daneman R, Rescigno M (2009) The gut immune barrier and the blood-brain barrier: are they so different? Immunity 31:722–735
Daneman R, Zhou L, Kebede AA et al (2010a) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468(7323):562–566
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
DÃaz-Coránguez M, Ramos C, Antonetti DA (2017) The inner blood-retinal barrier: cellular basis and development. Vis Res 139:123–137
Ebnet K (2017) Junctional Adhesion Molecules (JAMs): cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol Rev 97(4):1529–1554
Frank RN, Turczyn TJ, Das A (1990) Pericyte coverage of retinal and cerebral capillaries. Invest Ophthalmol Vis Sci 31:999–1007
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
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
Greene C, Campbell M (2016) Tight junction modulation of the blood brain barrier: CNS delivery of small molecules. Tissue Barriers 4(1):e1138017
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
Ikenouchi J, Sasaki H, Tsukita S et al (2008) Loss of occludin affects tricellular localization of tricellulin. Mol Biol Cell 19(11):4687–4693
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
Keaney J, Campbell M (2015) The dynamic blood-brain barrier. FEBS J 282(21):4067–4079
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
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
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
Krause G, Winkler L, Mueller SL et al (2008) Structure and function of claudins. Biochim Biophys Acta 1778:631–645
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
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
Mineta K, Yamamoto Y, Yamazaki Y et al (2011) Predicted expansion of the claudin multigene family. FEBS Lett 585(4):606–612
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
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
Peppiatt CM, Howarth C, Mobbs P et al (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443(7112):700–704
Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6:193–201
Reichenbach A, Bringmann A (2013) New functions of Müller cells. Glia 61(8):651–678
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
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
Trost A, Lange S, Schroedl F et al (2016) Brain and retinal pericytes: origin, function and role. Front Cell Neurosci 4(10):20
Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2:285–293
Vecino E, Rodriguez FD, Ruzafa N et al (2016) Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res 51:1–40
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/978-3-030-27378-1_54
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-27377-4
Online ISBN: 978-3-030-27378-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)