Retinal barriers blood-retina barrier

RPE plays numerous functions essential for proper structure and function of retinal photoreceptors. They include the maintenance of the blood-retina barrier, selective uptake and transport of nutrients from the blood to the retina and removal of waste products to the blood, enzymatic cleavage of P-carotene into vitamin A, storage of vitamin A and its metabolic transformations, phagocytosis and molecular renewal of POS, expression and secretion of growth factors and immunomodulatory cytokines (Aizman et al., 2007 Aleman et al., 2001 Crane et al., 2000a,b Elner et al., 2006 Holtkamp et al., 2001 Leuenberger et al., 2001 Lindqvist and Andersson, 2002 Maminishkis et al., 2006 Momma et al., 2003 Strauss, 2005). 

Crane, U, Wallace, CA, McKillop-Smith, S, and Forrester, JV, 2000b. CXCR4 receptor expression on human retinal pigment epithelial cells from the blood-retina barrier leads to chemokine secretion and migration in response to stromal cell-derived factor 1 alpha. J Immunol 165,4372-4378. 

Liversidge JM, Sewell HF, Forrester JV (1990) Interaction between Lymphocytes and cells of the blood-retina barrier Mechanisms of T lympohocyte adhesion to human retinal capillary endothelial cells and RPE cells in vitro. Immunology 71 390-396. 

Moldow B, Sander B, Larsoen M, et al. The effect of acetazolamide on passive and active transport of fluorescein across the blood-retina barrier in retinitis pigmentosa complicated by macular edema. Graefes Arch Clin Exp Ophthalmol 1998 236 881-889. 

The retina comprises two principal components, the non-neural retinal pigment epithelium and the neural retina. The retinal pigment epithelium is an essential component of the visual system both structurally and functionally. It is important for the turnover and phagocytosis of photoreceptor outer segments, the metabolism of retinoids, the exchange of nutrients between the photoreceptors, and the choroidal blood vessels and the maintenance of an efficient outer blood-retinal barrier. 

Figure 14.3 Integration plot of the initial uptake of [3H]adenosine by the retina after intravenous administration (A) and retinal uptake index (RUI) of [3H]adenosine and [3H]D-mannitol (B). A [3H]Adenosine (10 //.Ci/head) was injected into the femoral vein. B A test compound, [3H]adenosine or [3H]D-mannitol (10 //Ci/head), and a reference compound, [14C]n-butanol (0.1 //Ci/head), were injected into the common carotid artery in the presence or absence of 2 mM inhibitors. p < 0.05, significantly different from the control. Data from Biochimica et Biophysica Acta, 1758, Nagase et al., Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. 13-19, 2006, with permission from Elsevier.

T. Nakashima, M. Tomi, K. Katayama, M. Tachikawa, M. Watanabe, T. Terasaki, and K. Hosoya. Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier. J. Neumchem. 89 1454—1461... 

K. Hosoya, T. Kondo, M. Tomi, H. Takanaga, S. Ohtsuki, and T. Terasaki. MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier A possible route for delivery of monocarboxylic acid drugs to the retina. Pharm. Res. 18 1669-1676 (2001). 

The ocular endotamponades of the future could be a combination of tampo-nading and drug delivery device. Vitrectomy removes the natural vitreous after it has become opaque, inflamed, or unable to keep the retina in place. In many cases, the necessity to remove it is the result of retinal disorders, which are still existent after vitrectomy [50]. In equivalence to the blood-brain barrier, there is also a blood-retina barrier, with the effect that it is difficult to treat retinal disorders systemically. Therefore, the delivery of appropriate drugs via the vitreous cavity would open new treatment options. 

The blood-retinal barrier can be found in the posterior part of the eye. It prevents toxic molecules, plasma components, and water from entering the retina. It also forms a barrier for passage of systemically administered drugs into the vitreous, typically resulting in only 1-2% of the drug s plasma concentration in the intraocular tissues [24],... 

Tight junctional complexes zonula occludens ) in the retinal pigment epithelium prevent the ready movement of antibiotics and other drugs from the blood to the retina and vitreous. The retina is a developmental derivative of the neural tube wall and can be viewed as a direct extension of the brain it is not surprising that the blood-retinal barrier somewhat resembles the blood-brain barrier in form and function. Experimental evidence has shown that histamine does not alter the vascular permeability of the retina but does affect that of all other ocular tissues. The retina closely resembles the brain with respect to this trait. 

The capillaries of the retina are lined by continuous, close-walled, endothelial cells, which are the primary determinant of the molecular selectivity that is the major function of the blood-retinal barrier. Bruch s membrane is a prominent structure associated with the retinal-vitreous barrier, yet it contributes relatively little to the barrier s filtration properties. 

Bito LZ, DeRousseau CJ.Transport functions of the blood-retinal barrier system of the micro environment of the retina. In Cunha-Vaz J, ed. The blood-retinal barriers. New York Plenum Press, 1980 133-163. 

Neighboring RPE cells are connected by tight]unctions that help to create the blood/retinal barrier separating the neuro-sensory retina from fenestrated capillaries in the choroid. The basement membrane of RPE, together with the adjacent basement membrane of the choroid, forms a structure known as Bruch s membrane. RPE cells possess a number of organic and ion transporters to help move polar molecules across the blood retinal barrier. These include transporters for amino acids, folate, ascorbic acid, myo-inositol, organic anions, glucose and lactate. 

Blood is supplied to the retina by the central retinal artery and choroidal blood vessels (Oyster, 1999). The central retinal artery arises from the ophthalmic artery, w hich in turn branches off the internal carotid artery. Upon entering the retina, the central retinal artery branches into deep capillary beds in the INL and superficial capillary beds in the GCL. Endothelial cells of retinal capillaries are joined by tight junctions, contributing to the blood/retinal barrier. There is litde or no autonomic regulation of the retinal circulation blood flow through these capillaries is instead primarily controlled by autoregulation (Wangsa-Wirawan and Linsenmeier, 2003). Retinal capillaries drain into the central retinal vein. 

Greenwood J, Bamforth S, Wang Y, Devine L (1995) The blood-retinal barrier in immune- mediated diseases of the retina. In New Concepts of a Blood-Brain Barrier (Greenwood J, Begley DJ, Segal MB, eds), pp 315-326. New York Plenum Press. 

The retina represents an early evagination of the neural tube that remains outside the cranium after cytodifferentiation it has its own twofold blood-retinal barrier (BRB)... 

For its protection, the retina is physiologically and immunologically segregated from the rest of the body by the blood retinal barrier formed by tight junctions between vascular endothelial cells and RPE cells. Only small molecules can cross this barrier, making it difficult for many drugs to reach ocular tissue. In addition, intraocular tissue is an immune privileged site. This protects the ocular tissue from the innocent bystander effect of inflammation. 

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