Quantitative assessment of the permeability of the rat blood‐retinal barrier to small water‐soluble non‐electrolytes.

Lightman, Susan; Palestine, Alan G.; Rapoport, Stanley I.; Rechthand, Emanuel

doi:10.1113/jphysiol.1987.sp016667

Cited by 47 publications

(41 citation statements)

References 18 publications

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“…Using a variety of non-MRI but physiologically relevant methods and tracers in diabetic or galactose-fed rats, investigators have reported little or no change in BRB permeability in early diabetes (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). In contrast, in a study using a nonquantitative histological detection method with an endogenous tracer (extravasation of albumin), only a subset of diabetic rats is reported to develop some leakage (45)(46)(47).…”

Section: Brb Psmentioning

confidence: 99%

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

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There is a pressing need for retina-specific imaging biomarkers that robustly measure early (subclinical) changes in physiology, are linked to the histopathology responsible for vision loss, and, importantly, predict treatment efficacy. This review focuses on the following four MRI markers that we have developed and applied in preclinical and clinical settings: preretinal vitreous oxygen level (a steady-state biomarker of inner retinal oxygen tension); leakage of contrast agent into the vitreous (a steady-state biomarker of blood-retinal barrier permeability surface area product); change in preretinal vitreous oxygen tension during a hyperoxic provocation (a functional biomarker of vascular autoregulation); and retinal uptake of systemically administered manganese during a visual task (a functional biomarker of intraretinal ion regulation). We conclude that functional biomarkers are most promising for prognostic evaluation of treatment efficacy earlier in the course of retinopathy than is currently possible.

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Section: Brb Psmentioning

confidence: 99%

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

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“…Control values approximate previously published values. 6 ' 7 The BRB in SHR demonstrated a twofold increase in PA over that of controls (p<0.02), whereas the BBB showed no increase. There was no difference between plasma volumes for either the BRB or the BBB between the two strains.…”

Section: Chronic Hypertensionmentioning

confidence: 90%

“…3 To eliminate this possibility, the right eye was dissected while frozen to sample the aqueous, anterior vitreous, and posterior vitreous humors so as to estimate the anteriorposterior gradients of radioactivity within the eye to be worked out, as previously described. 6 The retinas, samples of occipital lobe, and all other samples were each put into preweighed scintillation vials, reweighed, and digested overnight at 50°C in 1 ml of M piperidine (Sigma). All samples including the plasma samples were prepared for scintillation counting by adding 10 ml of Ready Solv-MP scintillation cocktail (Beckman).…”

Section: Permeability To Sucrose In Wky and Shrmentioning

confidence: 99%

“…6 In the present study, we followed the method of Ohno et al 7 as described for the brain. A 20-minute time point after injection of [ 3 H]sucrose was chosen for killing the animals because at 20 minutes a unidirectional flux of sucrose occurs across the BBB and BRB in normal rats, as tissue concentrations are much lower than plasma concentrations at this time, making the possibility of backflux very small.…”

Section: Calculation Of Permeability To Sucrosementioning

confidence: 99%

“…A 20-minute time point after injection of [ 3 H]sucrose was chosen for killing the animals because at 20 minutes a unidirectional flux of sucrose occurs across the BBB and BRB in normal rats, as tissue concentrations are much lower than plasma concentrations at this time, making the possibility of backflux very small. 6 Because the amount of tracer in the tissue consists of two components, that which has crossed through the barrier into the tissue and that which still remains within the blood vessels, it is necessary to calculate the intravascular volume of these tissues, and the 5-minute [ l4 C]sucrose plasma space was used.…”

Section: Calculation Of Permeability To Sucrosementioning

confidence: 99%

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Assessment of the permeability of the blood-retinal barrier in hypertensive rats.

et al. 1987

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SUMMARY We assessed the permeability surface area products at the blood-retinal barrier and blood-brain barrier to sucrose (molecular weight, 340) and microperoxidase (molecular weight, 2000) following acute hypertension induced by metaraminol in Wistar-Kyoto rats (controls) and during chronic hypertension in spontaneously hypertensive rats. In acute hypertension, the permeability surface area product for sucrose was increased at the blood-retinal barrier and at the blood-brain barrier over control values (p<0.02), and the vessels became leaky to microperoxidase. In chronic hypertension, the permeability of the blood-retinal barrier to sucrose was increased over that in control animals (p<0.02), whereas the permeability of the blood-brain barrier was unaffected. Neither barrier leaked microperoxidase. These results indicate that the blood-brain barrier and the blood-retinal barrier are similarly affected in acute hypertension and that in chronic hypertension, the blood-brain barrier is unaffected whereas the blood-retinal barrier is rendered more permeable to small, but not large, solutes. 1 Changes in retinal blood vessels are apparent on clinical examination in humans with acute and chronic hypertension. Following an acute pressure rise, the blood-retinal barrier (BRB) can be shown to be breached using fluorescein angiography, but fiuorescein leakage usually is not apparent in chronic benign hypertension. Spontaneously hypertensive rats (SHR) have been used as an animal model to examine the effects of chronic hypertension. They manifest the characteristic renal lesions of arteriolar nephrosclerosis, 3 and their cerebral blood vessels demonstrate the same increased media thickness and larger vessel to lumen wall ratio

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Blood‐eye barriers in the rat: Correlation of ultrastructure with function

Stewart

Tuor

1994

J of Comparative Neurology

122

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The function of different vascular beds in the rat eye and brain was evaluated by measuring the transfer of a vascular tracer, 14C-alpha-amino-isobutyric acid, from blood to tissue. The density of vascular pores was measured in electron micrographs of perfusion-fixed, age-matched tissue to determine whether the differences in tracer transfer were paralleled by differences in ultrastructure. Tracer transfer in retina was approximately four times that in brain of the same animal. The transfer constant was not changed by the inclusion of cold alpha-amino-isobutyric acid, showing that transport across retinal vessels is not saturable, and indicating that, as in brain, transport is due to passive diffusion. Ultrastructurally, retinal vessels have a higher density of interendothelial junctions and of endothelial vesicles, both of which suggest higher vascular permeability. However, pericytes, which contribute to a second line of defence in the blood-brain barrier, are approximately four times as numerous in retina as in brain, and we suggest that in the retina, they act to compensate for a more permeable endothelial barrier. Ciliary body vessels had a high transfer of tracer, probably as a consequence of the fenestrations in their walls. Iridial vessels had a relatively low transfer of tracer, similar to that in retina even though a proportion of the interendothelial junctions in iridial vessels had expanded junctional clefts suggestive of open paracellular channels. However, both iris and ciliary body may lose tracer to the anterior chamber fluid, leading us to underestimate the vascular permeability in these sites.

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Quantitative assessment of the permeability of the rat blood‐retinal barrier to small water‐soluble non‐electrolytes.

Cited by 47 publications

References 18 publications

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Assessment of the permeability of the blood-retinal barrier in hypertensive rats.

Blood‐eye barriers in the rat: Correlation of ultrastructure with function

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