Transporter, retinal

Recently, a new mouse model was developed that allows us to examine photoresponses in an entirely opsin-free mouse model. Opsins require their chromophore, 11-cis-retinal, for function, and therefore, one obvious approach to create an opsin-free model would be to deprive mice of dietary vitamin A, rendering aU opsins nonfunctional, including rod and cone opsins as well as known and yet to be discovered novel opsins. This approach is not feasible in normal mice, because vitamin A is required during development, and adult mice have stored sufficient vitamin A in their Hver to last for the lifetime of the animals, even if they were put on a vitamin-A-free diet. The creation of the plasma retinol-binding protein mutant rbp) enables us to deplete ocular retinal in mice. The Rbp protein transports retinal from storage in the Hver to peripheral tissues. With the Rbp mutation, peripheral tissues such as the eye can be vitamin A depleted in 6 to 8 months. Therefore, we used the vitamin-A-depleted rhp mouse as an opsin-free model for circadian photoreception. 

C1C-6 is a late endosomal chloride transporter. Its disruption in mice led to lysosomal storage disease. C1C-7 is expressed in late endosomes and lysosomes. It needs Ostml as (3-subunit [3]. The disruption of either C1C-7 or Ostml in mice and man leads to severe osteopetrosis, retinal degeneration, and a severe lysosomal storage disease. ClC-7/Ostml is highly expressed in osteoclasts. In these cells, it is inserted together with the proton pump into the specialized plasma membrane ( ruffled border ) that faces the reabsorption lacuna. Osteoclasts are still present in C1C-7 knockout... 

The significance of the barrier function of membranes has been the topic of considerable research. The blood-brain barrier and the blood-retinal barrier are well understood, and the microscopic structures imparting and controlling barrier properties have been quite thoroughly investigated and the science reviewed [15, 154-155], The structures and functions of ocular membranes specific to transport associated with ophthalmic drug administration also have been topics of extensive research [15, 157-158],... 

Loane, E., J. M. Nolan et al. (2008). Transport and retinal capture of lutein and zeaxanthin with reference to age-related macular degeneration. Surv. Ophthalmol. 53(1) 68-81. 

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). 

Interestingly, carotenoids more abundant in the blood plasma than zeaxanthin, such as lycopene, P-carotene, and P-cryptoxanthin, do not accumulate in the retina. RPE cells express p,p-carotene 15,15 -monooxygenase (BCO), formerly known as P-carotene 15,l5 -dioxygcnase, an enzyme that catalyzes the oxidative cleavage of P-carotene into two molecules of all-trans-retinal (Aleman et al., 2001 Bhatti et al., 2003 Chichili et al., 2005 Leuenberger et al., 2001 Lindqvist and Andersson, 2002). Therefore it may be suggested that p -carotene transported into RPE-cells is efficiently cleaved into retinal molecules. BCO cleaves also P-cryptoxanthin (Lindqvist and Andersson, 2002), and its absence in the retina may also be explained by its efficient cleavage to retinoids. However, lycopene, often the most abundant carotenoid in human plasma, cannot serve as a substrate for BCO, and yet it is not detectable in the neural retina (Khachik et al., 2002). 

The greatest concentration of the macular pigment is present in the avascular part of the retina. This suggests that the RPE may play the predominant role in uptake and transport of xanthophylls to the photoreceptors. Moreover, about 25% of the total retinal xanthophylls are present in the POS (Rapp et al., 2000 Sommerburg et al., 1999), which, under normal conditions, are intimately associated with the RPE. This proximity lends further support to the hypothesis of a role for the RPE in the selective uptake of carotenoids into the retina. 

Bailey, KR, Ishida, BY, Duncan, KG, Kane, JP, and Schwartz, DM, 2004. Basal reverse cholesterol transport of retinal pigment epithelium cell digested photoreceptor outer segment lipids. Invest Ophthalmol Vis Sci 45, U721. 

Wang, N and Anderson, RE, 1993. Transport of 22 6n-3 in the plasma and uptake into retinal pigment epithelium and retina. Exp Eye Res 57, 225-233. 

Arriza, J. L., Eliasof, S., Kavanaugh, M. P., and Amara, S. G. (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci USA 94,4155 1160. 

Eliasof, S. and Jahr, C. E. (1996) Retinal glial cell glutamate transporter is coupled to an anionic conductance. Proc. Natl. Acad. Sci. USA 93,4153 4158. 

A variety of automatic voltage clamp devices with special modifications have been extensively utilized in electrophysiological studies of /sc in several ocular tissues including the amphibian corneal epithelium [42] and human fetal retinal pigment epithelium [43, 44], as well as non-ocular tissues like the rat tracheal epithelium [45], A strong temperature dependency and inhibitory effect of serosally instilled ouabain on the rabbit conjunctival /sc are characteristic of active ion transport driven by Na+/K+-ATPases in the conjunctiva [6, 7],... 

R. H. Quinn and S. S. Miller. Ion transport mechanisms in native human retinal pigment epithelium. Invest Ophthalmol Vis Sci 33 3513-3527 (1992)... 

Inner Blood-Retinal Barrier Transport Biology and Methodology... 

Keywords Inner blood-retinal barrier Transporter Influx transport Efflux transport Microdialysis Cell line Drug delivery... 

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