Studies on the permeability of the blood-retinal barrier

Shakib, Manoucher; Cunha-Vaz, Josè

doi:10.1016/s0014-4835(66)80011-8

Cited by 180 publications

(25 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Histamine markedly increased the vascular permeability of the various ocular tissues except for the retina. This behavior of the retinal vessels was similar only to what had previously been described for the cerebral vessels [4][5][6] . Following on our morphological studies and permeability measurements [4,7] , I proposed that the BRB should be regarded as consisting of 2 major components, the endothelium of the retinal blood vessels (inner BRB) and the retinal pigment epithelium (RPE) (outer BRB) [8] .…”

supporting

confidence: 84%

“…Morphological studies, using electron microscopy, where extremely rewarding, demonstrating the presence of zonulae occludentes in the retinal vessels between the endothelial cells, thereby showing that the retinal endothelial layer has an epithelium-like structure and offering an explanation for the permeability behavior of the retinal vessels [6] . This observation was later confirmed also for the brain vessels, providing support for our present understanding of the important role of the endothelial layers of the retinal and brain vessels in the BRB and BBB, respectively [9] .…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Cunha-Vaz

2017

Ophthalmologica

View full text Add to dashboard Cite

Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal fluid accumulation can be identified in specific retinal layers, clearly offering more information than previously obtained with fluorescein angiography. OCT angiography has become available, replacing much of the information yielded by fluorescein angiography in a noninvasive manner. However, OCT angiography cannot visualize the leakage, i.e., the alteration of the BRB. OCT-Leakage is able to identify the locations of increases in extracellular fluid in the different layers of the retina. The complementarity of these 2 methods is of potential great interest for the diagnosis and management of several retinal diseases in which the presence and amount of fluid, as a marker of severity and activity, is paramount to treatment and management decisions in clinical practice.

show abstract

supporting

confidence: 84%

mentioning

confidence: 99%

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Cunha-Vaz

2017

Ophthalmologica

View full text Add to dashboard Cite

show abstract

“…It is now generally accepted that such barriers are effective means by which tissues that perform specialized functions, such as the brain, can maintain a constant milieu and are shielded from the vagaries of the systemic circulation. With the advent of ultrastructural microscopy, it became evident that "occluding" junctions (zonulae occludentes) between endothelial or epithelial cells are the main anatomical features of these barriers (1)(2)(3)(4). However, knowledge of the physiological and biochemical concomitants of tissue barriers remains largely unknown.…”

mentioning

confidence: 99%

Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers.

Harik

Kalaria

Whitney

et al. 1990

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

View full text Add to dashboard Cite

We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by unmunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris.The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose.The physiological concept of blood-tissue barriers was formulated at the turn of this century. It is now generally accepted that such barriers are effective means by which tissues that perform specialized functions, such as the brain, can maintain a constant milieu and are shielded from the vagaries of the systemic circulation. With the advent of ultrastructural microscopy, it became evident that "occluding" junctions (zonulae occludentes) between endothelial or epithelial cells are the main anatomical features of these barriers (1-4). However, knowledge of the physiological and biochemical concomitants of tissue barriers remains largely unknown. The isolation behind barriers, preventing the simple diffusion of water-soluble substances into these tissues, necessitates transport systems in the microcirculation to ensure the steady availability of required nutrients, such as glucose.In 1965, Crone predicted that the brain capillary endothelium, which constitutes the blood-brain barrier, is particularly enriched with a glucose transporter, similar to that of human erythrocytes, that allows the selective, stereospecific, and saturable transport of large amounts of glucose from blood to brain (5, 6). Using ligand-binding methods (7,8) and, more recently, immunocytochemistry (9), we found that Crone's predictions were correct. Brain microvessels from several mammalian species, including man, are endowed with an unusually high density of glucose transporter protein (7-11) and messenger RNA (12, 13). In retrospect, these findings and Crone's predictions appear logical because brain capillaries, which account for <1% of the brain weight, have to transport glucose for the whole brain. In contrast, microvessels in brain regions that lack blood-brain barrier properties, such as those in the area postrema (9), and those of the heart and skeletal muscles (S.I.H., R.N.K., L.A., P.L., and G.P., unpublished observations) did not show a high density of glucose transporter. Recent clon...

show abstract

“…The quest for an in vivo assessment of BRB function has been a major objective of our research group and many others since the initial identification of the BRB in 1966 [3,4,7]. In this study, we have demonstrated the presence of indirect information on BRB status using noninvasive OCT data based on quantitative techniques.…”

Section: Discussionmentioning

confidence: 71%

Noninvasive Evaluation of Retinal Leakage Using Optical Coherence Tomography

et al. 2011

View full text Add to dashboard Cite

Purpose: To demonstrate the association between changes in the blood-retinal barrier (BRB) identified by fluorescein leakage and those in the optical properties of the human retina determined by optical coherence tomography (OCT) and show how these changes can be quantified and their location identified within the retina. Methods: Two imaging techniques were applied: the retinal leakage analyzer, to map BRB function into intact or disrupted regions, and OCT, to measure refractive index changes along the light path within the human ocular fundus. Results: A total of 140 comparisons were made, 77 between areas of regions receiving the same classification (intact or disrupted BRB) and 63 between areas of regions receiving distinct classifications, from 4 pathological cases: 2 eyes with nonproliferative diabetic retinopathy and 2 eyes with wet age-related macular degeneration. In all cases, the distribution of OCT data between regions of intact and regions of disrupted BRB, identified by the retinal leakage analyzer, was quantified and was statistically significantly different (p < 0.001). In addition, it was found that the differences could be localized in the retina to specific structural sequences. Conclusions: Using a novel method to analyze OCT data, we showed that it may be possible to quantify differences in the extracellular compartment in eyes with retinal disease and alterations of the BRB. Based on quantitative techniques, our findings demonstrate the presence of indirect information on the BRB status within noninvasive OCT data.

show abstract

Studies on the permeability of the blood-retinal barrier

Cited by 180 publications

References 14 publications

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers.

Noninvasive Evaluation of Retinal Leakage Using Optical Coherence Tomography

Contact Info

Product

Resources

About