Disease relevance of Blood-Retinal Barrier

• Aldose-reductase inhibition may play an important role in stabilization of the blood-retinal barrier in early diabetic retinopathy [1].
• It is known that vascular endothelial growth factor causes retinal neovascularization and a breakdown of the blood-retinal barrier; how advanced glycation end products affect the retina, however, remains largely unclear [2].
• The antihypertensive treatment induced a significant reduction (p less than 0.05) in: blood pressure from 152/97 +/- 14/8 mmHg to 134/82 +/- 11/6 mmHg; blood-retinal barrier leakage of fluorescein from 2.4 +/- 1.1 to 1.4 +/- 0.5.10(-7) cm/second; albuminuria from 1391 (range: 168-4852) micrograms/min to 793 (range: 35-2081) micrograms/min [3].
• 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 less than 0.02), and the vessels became leaky to microperoxidase [4].
• Parallel in vivo studies of nondiabetic mice assessed the effect of intraperitoneal delivery of AGE-Alb on ICAM-1 mRNA expression, NFkappaB DNA-binding activity, leukostasis, and blood-retinal barrier breakdown [5].

High impact information on Blood-Retinal Barrier

• Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF [6].
• Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect [6].
• The blood-retinal barrier: leucine transport by the retinal pigment epithelium [7].
• AR deficiency led to fewer retinal blood vessels with IgG leakage, suggesting that AR may contribute to blood-retinal barrier breakdown [8].
• These results suggest that cytokine-induced upregulation of MMP-9 expression by the CNS vascular endothelium may play a role in the pathogenesis of blood-brain and blood-retinal barrier breakdown in vivo [9].

Chemical compound and disease context of Blood-Retinal Barrier

• Breakdown of blood. Retinal barrier in RCS rats with inherited retinal degeneration [10].
• The sensitivity of RPE metabolism to glucose fluctuations may relate to changes in the blood-retinal barrier that are known to occur in diabetes (e.g. macular edema) [11].
• For all animals the blood-retinal barrier remained impermeable to either carboxyfluorescein or Evans blue, indicating a functionally intact tight junctional barrier during hypercapnia [12].
• Calcium dobesilate stabilizes blood-retinal barrier in patients with diabetic retinopathy and possesses antioxidant properties in the retinas of rats with streptozotocin-induced diabetes, exposed ex vivo to ischemia-reperfusion [13].
• We have also confirmed that this edema is inhibited by topically administered indomethacin, which proves that in the rupture of blood-retinal barriers during the vitrectomy, prostaglandins play an important role [14].

Biological context of Blood-Retinal Barrier

• Kinetics of glucose transport across the blood-retinal barrier [15].
• Active transport of fluorescein across the blood-retinal barrier in the direction of vitreous to blood does not seem to be significant within the first 2 hr after fluorescein injection [16].
• Taken together, our observations indicate that a leakage of serum into the retina compromises the regulation of [K+]o by Müller cells; however, when plasma enters the retina at sites of a breakdown in the blood-retinal barrier, these glia can maintain K+ homeostasis while reducing the potentially neurotoxic levels of glutamate [17].
• By performing vitreous fluorophotometry and fluorescein angiography, it is possible to quantitate two major components of diabetic maculopathy: breakdown of the blood-retinal barrier and macular ischemia, both of which are highly correlated with visual acuity [18].
• CONCLUSION: We conclude that increased vascular permeability for plasma proteins induced by VEGF in blood-retinal barrier endothelium is predominantly caused by a mechanism involving active trans-endothelial transport via pinocytotic vesicles and not by formation of endothelial fenestrations or VVOs [19].

Anatomical context of Blood-Retinal Barrier

• PURPOSE: The GLUT1 glucose transporter mediates glucose entry into the endothelial cells of the inner blood-retinal barrier (BRB) [20].
• Indomethacin significantly prevented disruption of the blood-aqueous barrier at 2 and 3 months and significantly prevented disruption of the blood-retinal barrier at 3 months [21].
• When a retina with an impaired blood-retinal barrier (BRB) is illuminated with blue light (480 mm) after intravenous fluorescein (F) injection, photoreceptors are presumed to be stimulated not only by the original blue light but also by a green one (520 mm) that is emitted by the leaked F [22].
• Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat [23].
• During retinal disease, glial cell production of active TGF-beta may contribute to breakdown of the blood-retinal barrier by stimulating endothelial cell MMP-9 production [24].

Associations of Blood-Retinal Barrier with chemical compounds

• The clinical study showed that only the posterior vitreous concentration of fluorescein is relevant in the evaluation of the blood-retinal barrier [25].
• Permeability-surface-area products (PA) for sucrose at the blood-retinal barrier (BRB) were determined with quantitative in vivo techniques and compared in control rats, rats fed a 50% galactosemic diet, and rats fed a diet containing both galactose and the aldose reductase inhibitor sorbinil [26].
• Sucrose infused intravenously prior to sampling the tissue did not traverse the outer blood retinal barrier of the normal or the diabetic retina [27].
• Sensitive blood-retinal barrier breakdown quantitation using Evans blue [28].
• Sixty days after administration, the animals were killed, and retinal PGE2 secretion, VEGF protein, and blood-retinal barrier leakage were estimated [29].

Gene context of Blood-Retinal Barrier

• We have therefore examined the production of RANTES by cultured human retinal pigment epithelial cells (RPE), which form a part of the blood-retinal barrier, in response to cytokines likely to be present in the microenvironment [30].
• CONCLUSION: IL-6 derived from blood during the breakdown of the blood-retinal barrier (BRB) and produced by RPE cells and hematogenous sIL-6R cause RPE proliferation [31].
• Periocular gene transfer of sFlt-1 suppresses ocular neovascularization and vascular endothelial growth factor-induced breakdown of the blood-retinal barrier [32].
• It is likely that the retina contains a mechanism for the degradation of hemopexin-bound heme since the blood-retinal barrier also precludes the exit of heme-hemopexin from the retina [33].
• These results suggest that AR is involved in the functional regulation of OAT3 at the BBB, but not at the inner blood-retinal barrier (iBRB), and this regulation is not affected by gender [34].

Analytical, diagnostic and therapeutic context of Blood-Retinal Barrier

• The integrity of the blood-retinal barrier was assessed by intravenous injection of Evans blue [35].
• Periocular celecoxib microparticles are useful sustained drug delivery systems for inhibiting diabetes-induced elevations in PGE2, VEGF, and blood-retinal barrier leakage [29].
• Pathophysiology of the blood-retinal barrier in experimental diabetes. Vitreous fluorophotometry using carboxyfluorescein and fluorescein [36].
• Since, fluorescein angiography is a rather crude method of detecting abnormalities of the blood-retinal barriers, vitreous fluorometry in addition is suggested [37].
• Effect of argon laser photocoagulation on fluorescein transport across the blood-retinal barrier [38].

References