Elsevier

Brain Research

Volume 629, Issue 2, 3 December 1993, Pages 218-224
Brain Research

The relationship of astrocyte-like cells to the vessels that contribute to the blood-ocular barriers

https://doi.org/10.1016/0006-8993(93)91323-KGet rights and content

Abstract

Brain capillaries form a selective interface, the blood-brain barrier (BBB), between the neural parenchyma and the blood. The factors which regulate this interface are poorly understood. Both the iris and retina possess vascular beds that express some BBB characteristics; therefore, they provide attractive models to further our understanding of how blood-tissue interfaces are regulated. We have determined whether three BBB markers: the transferrin receptor, P-glycoprotein, and gamma-glutamyl transpeptidase (γ-GTP), can be localized in the capillaries of the rat retina and iris. We have also compared, in retina and iris, the relationship which GFAP-positive cells have with the blood vessels to the expression of the three BBB markers by the vessels. Immunocytochemistry revealed that capillaries throughout the retina express P-glycoprotein and the transferrin receptor. Retinal vessels do not show detectable γ-GTP activity. GFAP-positive cells ensheath capillaries in the nerve fibre layer of the retina. Of the three BBB characteristics we examined, iridial vessels expressed only one of them; P-glycoprotein. In the iris, GFAP-positive cells do not ensheath capillaries. From our results we conclude that all BBB characteristics do not have to be expressed and regulated in capillaries as a unit. Our results, in combination with those of earlier studies, suggest that the expression of some BBB features does not require intimate contact between capillaries and astrocytes or astrocyte-like cells. Barrier maintenance appears to be a complex process which involves the integration of several factors.

References (56)

  • ShineH.D. et al.

    Immunocytochemical localization of gamma-glutamyl transpeptidase in the rat CNS

    Brain Res.

    (1981)
  • StewartP.A.

    Histochemical absence of gamma-glutamyl transpeptidase in chick brain capillary endothelium

    Exp. Neurol.

    (1980)
  • StewartP.A. et al.

    Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: A study using quail-chick transplantation chimeras

    Dev. Biol.

    (1981)
  • SzalayJ. et al.

    Permeability of iridial blood vessels

    Exp. Eye Res.

    (1975)
  • TakakuraY. et al.

    Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. II. Effects of conditioned media from astroglial and glioma cells

    Biochem. Biophys. Acta

    (1991)
  • TontschU. et al.

    Glial cells and neurons induce blood-brain barrier related enzymes in cultured cerebral endothelial cells

    Brain Res.

    (1991)
  • AlbertZ. et al.

    Studies of gamma-glutamyltranspeptidase activity and its histochemical localization in the central nervous system of man and different species

    Acta Histochem.

    (1966)
  • BellhornR.W.

    Permeability of blood-ocular barriers of neonatal and adult cats to fluorescein-labeled dextrans of selected molecular sizes

    Invest. Ophthalmol. Vis.

    (1981)
  • Belloni-OliviL. et al.

    Retinal microvessels express less gamma-glutamyl transpeptidase than brain microvessels

    Curr. Eye Res.

    (1992)
  • BertlerA. et al.

    The localization of monoaminergic blood-barriers mechanisms

    Pharmacol. Rev.

    (1966)
  • Bjo¨rklundH. et al.

    Glial fibrillary acidic protein-like immunoreactivity in the iris: development, distribution, and reactive changes following transplantation

    J. Neurosci.

    (1984)
  • BouchardC. et al.

    Are close contacts between astrocytes and endothelial cells a prerequisite condition of a blood-brain barrier?, The rat subfornical organ as an example

    Biol. Cell

    (1989)
  • BrightmanM.W. et al.

    Junctions between intimately apposed cell membranes in the vertebrate brain

    J. Cell Biol.

    (1969)
  • Chan-LingT. et al.

    Factors determining the migration of astrocytes into the developing retina: migration does not depend on intact axons or patent vessels

    J. Comp. Neurol.

    (1991)
  • Chan-LingT. et al.

    Factors determining the morphology and distribution of astrocytes in the cat retina: a ‘contact-spacing’ model of astrocyte interaction

    J. Comp. Neurol.

    (1991)
  • Cunha-VazJ.G. et al.

    Studies on the permeability of the blood-retinal barrier. I. On the existence, development, and site of a blood-retinal barrier

    Br. J. Ophtalmol.

    (1966)
  • EnnisS.R. et al.

    Sucrose permeability of the blood-retinal and blood-brain barriers. Effects of diabetes, hypertonicity and iodate

    Invest. Ophthalmol. Vis. Sci.

    (1986)
  • FrankR.N. et al.

    Pericyte coverage is greater in the retinal than in the cerebral capillaries of the rat

    Invest. Ophthalmol. Vis. Sci.

    (1987)
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