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

Cunha-Vaz, Josè; Shakib, Manoucher; Ashton, Norman

doi:10.1136/bjo.50.8.441

Cited by 171 publications

(62 citation statements)

References 14 publications

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“…The only other structure which could form a barrier to the passage of the dye is the basement membrane. This concept is supported by the same electron microscopical studies, which show that the blood-retinal barrier to large molecules is located in the endothelial layer of the retinal vessels (Ashton, 1965;Cunha-Vaz et al 1966). The barrier is formed by a tightly packed layer of endothelial cells joined together by junctional complexes which completely seal the intercellular spaces.…”

Section: Methodssupporting

confidence: 62%

“…1) to be completely free from surrounding glia and in direct contact with the vitreous humour (Ashton, 1965;Cunha-Vaz et al 1966). If the vessels are responsible for the active transport of fluorescein, then the endothelial cells must be the site of this activity because they form the only complete cellular layer interposed between the blood and vitreous body.…”

Section: Methodsmentioning

confidence: 99%

“…Studies on the permeability of the retinal capillaries (Ashton, 1965; Cunha-Vaz, Shakib & Ashton, 1966) showed that they offered an extremely high resistance to the passage of certain large molecules, a property which is shared only by the vessels of the brain. It was wished to widen these investigations to more diffusible substances, and fluorescein was chosen because techniques were available for measuring its concentration and concentration gradient in the vitreous body of the living rabbit (Kaiser & Maurice, 1964).…”

Section: Introductionmentioning

confidence: 99%

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The active transport of fluorescein by the retinal vessels and the retina

Cunha-Vaz¹,

Maurice²

1967

The Journal of Physiology

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213

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SUMMARY1. The movement of fluorescein across the retinal surface of the rabbit's eye was estimated by measuring the concentration gradient of the dye in the vitreous body. These measurements were made in vivo by means of a slit-lamp fluorophotometer, or were taken from frozen sections ofenucleated eyes.2. In the normal eye, fluorescein does not pass from the blood to the vitreous body across any part of the retina. When injected into the vitreous body it passes rapidly out across the entire retinal surface, even against a very large concentration gradient.3. A variety of metabolic and competitive inhibitors, effective in blocking organic anion transport in the kidney and liver, tend to abolish this unidirectional movement of fluorescein across the retina.4. The region occupied by the retinal vessels is more sensitive to inhibition than other areas of the retina. Occlusion of the vessels by diathermy prevents the exchange of fluorescein in this region.5. It appears, then, that there is an active transport of organic anions out of the vitreous body, both by the retinal capillaries and by the retina itself. The latter system is probably located in the pigment epithelium and seems to be carried forward to the rear surface of the iris.6. Since the walls of the retinal vessels of the rabbit are freely in contact with the vitreous body, the active transport must take place across the capillary endothelial cells themselves. These vessels have structural and permeability characteristics found only in the central nervous system and it is to be presumed that the anion transport system is shared by the capillaries of the brain.

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Section: Methodssupporting

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The active transport of fluorescein by the retinal vessels and the retina

Cunha-Vaz¹,

Maurice²

1967

The Journal of Physiology

Self Cite

213

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“…Non-specific transport between the circulating blood and neural retina is restricted by the tight junction formed at the inner and outer BRB, and the membrane transporters expressed in these responsible cells are suggested to contribute to selective transport between the circulating blood and neural retina. [12][13][14][15] Biochemical studies showed that taurine is the most abundant free amino acid in the retina (12 mM in rats), and its retinal concentration is much greater than its concentration in the serum (100-300 µM) [16][17][18][19] (Fig. 1).…”

Section: Taurine Transport Across the Brbmentioning

confidence: 99%

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Kubo

Akanuma

Hosoya

2016

Biological & Pharmaceutical Bulletin

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Cumulative studies showed that taurine (2-aminoethanesulfonic acid) contributes to a variety of physiological events. Transport study suggested the cellular taurine transport in an Na -and Cl -dependent manner, and the several members of SLC6A family have been shown as taurine transporter. At the inner blood-retinal barrier (BRB), taurine transporter (TauT/SLC6A) is involved in the transport of taurine to the retina from the circulating blood. The involvement of TauT is also suggested in γ-aminobutyric acid (GABA) transport at the inner BRB, and its role is assumed in the elimination of GABA from the retinal interstitial fluid. In the retina, taurine is thought to be a major organic osmolyte, and its influx and efflux through TauT and volume-sensitive organic osmolyte and anion channel (VSOAC) in Müller cells regulate the osmolarity in the retinal microenvironment to maintain a healthy retina. In the liver, hepatocytes take up taurine via GABA transporter 2 (GAT2/SLC6A13, the orthologue of mouse GAT3) expressed at the sinusoidal membrane of periportal hepatocytes, contributing to the metabolism of bile acid. Site-directed mutagenesis study suggests amino acid residues that are crucial in the recognition of substrates by GATs and TauT. The evidence suggests the physiological impact of taurine transporters in tissues.

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“…Since the synthesis of NO has been shown to be dependent on the availability of extracellular Larginine (Kurz and Harrison 1997), membrane transport of extracellular L-arginine represents one of the rate-limiting steps in establishing the local NO level and, thus, in NO action. The nutrient supply to the retina from the circulating blood is regulated by the blood-retinal barrier (BRB), which is composed of retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (RPE, outer BRB) (Cunha-Vaz et al 1966;Hosoya and Tomi 2005). L-Arginine transport at the inner BRB plays an especially important role in regulating the retinal NO level, since it can directly regulate NO production by eNOS and, also, the inner twothirds of the human retina is nourished by a direct blood supply through the inner BRB (Harris et al 2001).…”

mentioning

confidence: 99%

Cationic amino acid transporter 1‐mediated l‐arginine transport at the inner blood–retinal barrier

Tomi

Kitade

Hirose

et al. 2009

Journal of Neurochemistry

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pigment epithelial cells; RVEC, retinal vascular endothelial cells; siRNA, small interfering RNA; TR-iBRB2, conditionally immortalized rat retinal capillary endothelial cell line. AbstractThe purpose of this study was to identify the transporter mediating L-arginine transport at the inner blood-retinal barrier (BRB). The apparent uptake clearance of [ 3 H]L-arginine into the rat retina was found to be 118 lL/(minAEg retina), supporting a carrier-mediated influx transport of L-arginine at the BRB. transporter (CAT) 1 mRNA was 25.9-and 796-fold greater than that of CAT3 in TR-iBRB2 and magnetically isolated rat retinal vascular endothelial cells, respectively. The expression of CAT1 protein was detected in TR-iBRB2 cells and immunostaining of CAT1 was observed along the rat retinal capillaries.In conclusion, CAT1 is localized in retinal capillary endothelial cells and at least in part mediates L-arginine transport at the inner BRB. This process seems to be closely involved in visual functions by supplying precursors of biologically important molecules like nitric oxide in the neural retina.

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

Cited by 171 publications

References 14 publications

The active transport of fluorescein by the retinal vessels and the retina

The active transport of fluorescein by the retinal vessels and the retina

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Cationic amino acid transporter 1‐mediated l‐arginine transport at the inner blood–retinal barrier

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