The structural basis of the blood-ocular barriers

Raviola, Giuseppina

doi:10.1016/s0014-4835(77)80009-2

Cited by 277 publications

(122 citation statements)

References 52 publications

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“…In the studies shown in Figs. [1][2][3][4] less than 5% of the radiolabel present in the isolated incubated microvessels was precipitable with trichloroacetic acid after 30 min of incubation.…”

Section: Methodsmentioning

confidence: 99%

“…An indication that the microvascular endothelium, with its tight junctions, was the structural entity responsible for this barrier action and not the astrocytic processes adjacent to the microvessels was obtained when it was demonstrated that intraventricularly injected horseradish peroxidase appeared in the pericapillary space (3). Similarly, the impenetrability of the retinal microvasculature to dyes and electron-dense tracers (4) has been attributed to its endothelial tight junctions. In addition, both the retinal and brain microvascular endothelium have low rates of vesicle formation which further decreases the movement of molecules across this cell layer (5).…”

Section: Respectivelymentioning

confidence: 99%

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Isolated microvessels: the blood-brain barrier in vitro.

Hjelle¹,

Baird-Lambert²,

Cardinale³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

111

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Isolated bovine retinal and brain microvessels, exhibiting a patent lumen, were used to study the contribution of the microvasculature to the blood-brain and blood-retina barriers. The diffusion marker, sucrose, was taken up slowly by the isolated microvessels in contrast to leucine, tyrosine, and valine which were taken up at a considerably faster rate. Uptake of leucine was temperature dependent but resistant to inhibition by ouabain and sodium azide. The large neutral amino acids exhibited stereospecificity and cross-competition for uptake by the isolated microvessels. The apparent Kms for uptake for tyrosine, leucine, and valine were 111 M, 133 MM, and 500 M&M, respectively.The penetration into or removal of a substance from the central nervous system is a function of the interaction between that substance and the various brain barrier systems (1). These systems include the partitions between brain regions, various enzymatic barriers, the clearance and sink actions of the cerebrospinal fluid, choroid plexus and pial vessel transport, and partitioning at the blood-brain interface. From numerous morphological studies using dyes and electron-dense tracers, the barrier to the passage of substances from the blood into the brain has been thought to reside at the level of the intracerebral microvasculature (2). An indication that the microvascular endothelium, with its tight junctions, was the structural entity responsible for this barrier action and not the astrocytic processes adjacent to the microvessels was obtained when it was demonstrated that intraventricularly injected horseradish peroxidase appeared in the pericapillary space (3). Similarly, the impenetrability of the retinal microvasculature to dyes and electron-dense tracers (4) has been attributed to its endothelial tight junctions. In addition, both the retinal and brain microvascular endothelium have low rates of vesicle formation which further decreases the movement of molecules across this cell layer (5). Additional involvement of the cerebral microvasculature in blood-brain partitioning has been demonstrated by in situ carotid artery injection quickly followed by decapitation and determination of brain extraction of the injected test substance (6). Because of the short time interval between injection and decapitation, it has been assumed that the extraction of the test substance was an index of microvascular activity.To more directly characterize the role of the cerebral microvasculature in the partitioning of small molecules between the blood and the brain and to develop methods for the study of such phenomena in vitro, we examined isolated intracerebral bovine brain microvessels and the anatomically similar retinal microvessels for their abilities to exclude certain polar substances and to transport large neutral amino acids. Beef brains and enucleated eyes from yearling animals were obtained from a slaughterhouse, packed in ice, and taken to the laboratory within 30 min of death. MATERIALS AND METHODS MaterialsPreparation of Microvessels...

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Section: Methodsmentioning

confidence: 99%

Section: Respectivelymentioning

confidence: 99%

Isolated microvessels: the blood-brain barrier in vitro.

Hjelle¹,

Baird-Lambert²,

Cardinale³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

111

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show abstract

“…The superficial plexus lies immediately beneath the inner limiting membrane, while the deep plexus permeates the inner nuclear layer. The endothelial cells lining the vessels in the retinal capillary plexuses form tight junctions and provide an important part of the blood-retinal barrier, while the choroidal vessels are fenestrated, lacking this barrier (Raviola, 1977;Campochiaro, 2000). At the choroid/retina interface, barrier function is provided by tight junctions between adjacent retinal pigment epithelial cells.…”

Section: Development Of the Retinal Vasculaturementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

612

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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“…The OLM has long been thought to be the primary structure responsible for the adhesion between Muller cells and photoreceptors and consequently the integrity of the ONL (Dowling, 1970;Raviola, 1977). It is thus tempting to first determine if Nok is functionally related to the OLM.…”

Section: Nok Is Required For the Establishment And/or Maintenance Of mentioning

confidence: 99%

“…The packing of photoreceptors into a single cellular layer requires precise coordination of photoreceptor adhesion. Among the possible subcellular structures that are responsible for the assembly of the ONL, the outer limiting membrane (OLM) has attracted much attention because of its easy identification under EM and light microscopes (Dowling 1970;Raviola 1977). …”

Section: Introductionmentioning

confidence: 99%

Nok plays an essential role in maintaining the integrity of the outer nuclear layer in the zebrafish retina

Wei

Zou

Takechi

et al. 2006

Experimental Eye Research

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Proper visual function of the vertebrate retina requires the maintenance of the integrity of the retinal outer nuclear layer (ONL), which is often affected in many blinding human retinal diseases.While the structural integrity of the ONL has long been considered to be maintained primarily through the outer limiting membrane (OLM), we have little knowledge on the development and maintenance of the OLM itself. Here, by analyzing the adhering properties of photoreceptors in zebrafish N-cad and nok mutants, we demonstrated for the first time that the nok gene is essential for the establishment and/or maintenance of the OLM. In addition, our results imply the possibility that Nok, Crumbs, and their associated proteins may constitute a type of photoreceptor-photoreceptor junctional complex that has not been described before. Thus, our study provides novel insights into the mechanisms by which the integrity of the ONL is maintained in the vertebrate retina.

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The structural basis of the blood-ocular barriers

Cited by 277 publications

References 52 publications

Isolated microvessels: the blood-brain barrier in vitro.

Isolated microvessels: the blood-brain barrier in vitro.

Vascular endothelial growth factor in eye disease

Nok plays an essential role in maintaining the integrity of the outer nuclear layer in the zebrafish retina

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