Retina lipoproteins

Carotenoids are also present in animals, including humans, where they are selectively absorbed from diet (Furr and Clark 1997). Because of their hydrophobic nature, carotenoids are located either in the lipid bilayer portion of membranes or form complexes with specific proteins, usually associated with membranes. In animals and humans, dietary carotenoids are transported in blood plasma as complexes with lipoproteins (Krinsky et al. 1958, Tso 1981) and accumulate in various organs and tissues (Parker 1989, Kaplan et al. 1990, Tanumihardjo et al. 1990, Schmitz et al. 1991, Khachik et al. 1998, Hata et al. 2000). The highest concentration of carotenoids can be found in the eye retina of primates. In the retina of the human eye, where two dipolar carotenoids, lutein and zeaxan-thin, selectively accumulate from blood plasma, this concentration can reach as high as 0.1-1.0mM (Snodderly et al. 1984, Landrum et al. 1999). It has been shown that in the retina, carotenoids are associated with lipid bilayer membranes (Sommerburg et al. 1999, Rapp et al. 2000) although, some macular carotenoids may be connected to specific membrane-bound proteins (Bernstein et al. 1997, Bhosale et al. 2004). 

Recent data indicate that SR-BI is a nonspecific receptor for many lipophilic molecules (Lorenzi et al., 2008 Reboul et al., 2007b). Apart from HDLs, rodent SR-BI also binds to LDL, VLDL, acetylated LDL, oxidized LDL, and maleylated bovine serum albumin. SR-BII has a similar ligand specificity and function to that of SR-BI (Webb et al., 1998). However, it has been shown that vitamin E (which like carotenoids is carried in the bloodstream mainly by LDL and HDL) is transported more efficiently into the endothelial cells from HDLs than from LDLs (Balazs et al., 2004 Kaempf-Rotzoll et al., 2003 Mardones and Rigotti, 2004). This is in striking contrast to cholesterol, which is taken up much more efficiently from LDLs than HDLs by the RPE to the retina (Tserentsoodol et al., 2006b). It remains to be shown which lipoproteins are the main carriers for carotenoids transported from blood into the RPE. 

These data suggest that one of possible mechanisms of carotenoid delivery to the neural retina may involve lipoprotein uptake from the basal side of the RPE followed by its retro-endocytosis on the apical site (Lorenzi et al., 2008). Alternatively, the endocytosed lipoprotein may be degraded in the RPE followed by secretion of certain lipophilic components from the lipoprotein at the apical site. Due to low solubility of carotenoids in aqueous solutions, it may be suggested that they are secreted already bound to a protein or that an acceptor protein is available in the interphotoreceptor matrix and/or POS. 

ApoC-I is expressed mainly in liver but also in lung, skin, testis, spleen, neural retina, and RPE. Its multiple functions include the activation of lecithin cholesterol acyltransferase (LCAT) and the inhibition, among others, of lipoprotein and hepatic lipases that hydrolyze triglycerides in particle cores. Notably, both LCAT and lipoprotein lipases are expressed in RPE and choroid (Li et al., 2006). Moreover ApoC-I has been shown to displace ApoE on the VLDL and LDL and thus hinder their binding and uptake via their corresponding receptors (Li et al., 2006). 

ApoC-II is expressed in liver and intestine, and both the neural retina and RPE (Li et al., 2006). In contrast to ApoC-I, it can function as an activator of lipoprotein lipase. Similar to ApoA-I, ApoA-II, and ApoE, in the absence of lipid to stabilize its structure, ApoC-II forms amyloid assemblies. 

The expression of all these apo-lipoproteins by the RPE, and its ability to form lipoprotein particles suggest that these newly formed lipoproteins may be involved in the transport of lipophilic molecules, including carotenoids, from the RPE to the neural retina and/or to the choroidal blood supply. Testing the roles of apolipoproteins and lipoprotein particles in carotenoid secretion from the RPE is another subject awaiting experimental investigation. 

While it may be speculated that in the RPE both lipoprotein and/or scavenger receptors are likely to be involved in carotenoid uptake from the blood, it is not clear what mechanism(s) are responsible for carotenoid transport through the RPE into the neural retina. Also, it is not clear what mechanism(s) are responsible for selective accumulation in the retina of only two carotenoids. 

The neural retina expresses several lipoprotein receptors including SR-BI, SR-BII (Tserentsoodol et al., 2006a,b), and VLDL receptor (VLDLR) (Hu et al., 2008). Thus, carotenoid flow through the RPE and further transport in the neural retina may also be mediated by lipoprotein receptors (Tserentsoodol et al., 2006a,b). SR-BI and SR-BII have been found to be localized mainly to the ganglion cell layer and POS in the monkey retina (Tserentsoodol et al., 2006a). 

Astaxanthin has been suggested as a potential dietary supplement to improve retinal function (Hussein et al., 2006 Parisi et al., 2008). While normally astaxanthin is not present in human plasma, a high dose of dietary astaxanthin does result in its appearance in appreciable concentrations within the plasma where it is bound mainly to the lipoproteins, VLDL, LDL, and HDL (Coral-Hinostroza et al., 2004). To our knowledge, to date there is no report identifying astaxanthin in human retina. 

Tserentsoodol, N, Sztein, J, Campos, M, Gordiyenko, NV, Fariss, RN, Lee, JW, Fhesler, SJ, and Rodriguez, IR, 2006b. Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-... 

Phosphatidylcholine (PC) is the main phospholipid in all mammalian cells (40-50%) and lipoproteins. As a consequence, most oxidized phospholipids detected in mammalian tissues contain a choline head group. In addition to oxidized PC (oxPC), oxidized phosphatidylserine (oxPS) and phosphatidy-lethanolamine (oxPE) have been detected. The latter was found in the retina, which is a tissue containing high amounts of phosphatidylethanolamine (Gugiu et ah, 2006), while OxPS was reported to be present on the surface of apoptotic cells (Kagan et ah, 2002 Matsura et ah, 2005). 

Unesterified xanthophylls such as lutein in its pure form are absorbed by mucosal cells and subsequently appear unchanged in the circulation and peripheral tissue. Esterified xanthophylls must be de-esterified to their pure form before uptake [34, 45]. The xanthophylls are packaged as plasma lipoproteins by the Uver, released into the systemic circulation, and absorbed by a range of tissues including liver, lung, adipose, skin, prostate, and macula [34,46]. Their major storage site is adipose tissue [34, 47], so much so that a negative correlation between the adipose tissue L concentration and the amount of L and Z in the retina has been reported in women [48]. 

In the long term, failure of glycaemic control and a persistently high plasma glucose concentration results in damage to capillary blood vessels (especially in the retina, leading to a risk of blindness), kidneys and peripheral nerves (leading to loss of sensation) and the development of cataracts in the lens of the eye and abnormal metabolism of plasma lipoproteins (which increases the risks of atherosclerosis and ischaemic heart disease). Two mechanisms have been proposed to explain these effects ... 

The only two cases where a repetitive pattern was shown by X-ray diffraction concerned the chloroplast membrane (von Kreutz and Mencke, 1962 von Kreutz, 1964) and the photoreceptor membranes of the frog retina (Blasie et al., 1969). In both cases the observed patterns concerned protein units these, in the first case, measured 35 A and formed a planar array (see Fig. 10a) at the surface of a lipid layer. In the second case, the units were cylindrical molecules of rho-dopsin the evidence clearly excluded the possibility for these particles to be spherical lipoproteins or lipid micelles since their cross-sectional electron density was not characteristic of these phases, but definitely that of protein. 

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