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transporters: ABCA6, ABCA8, and ABCA10 (van Soest et al., 2007). The functions of those
transporters are not well understood. ABCA6 is also expressed in liver, lung, heart, and brain and
is believed to be involved in lipid homeostasis (Kaminski et al., 2001). ABCA8 is also expressed
in human brain and in isolated fetal brain neurons and astrocytes, and it is involved in transport of
lipophilic molecules, including the bioactive lipid, leukotriene C4 (Kim et al., 2008). In the mouse
brain, ABCA8 was identii ed in the choroid plexus (Matsumoto et al., 2003), which is responsible
for the formation of the blood-cerebrospinal l uid barrier. ABCA10 is ubiquitously expressed,
with the highest gene expression levels detectable in the heart, brain, and the gastrointestinal tract,
and it is believed to be involved in lipid homeostasis (Wenzel et al., 2003).
It may be suggested that as a result of lipoprotein uptake a variety of carotenoids enter the RPE
and subsequently lutein and zeaxanthin are transported into the neural retina, provitamin A carote-
noids are metabolized to form vitamin A within the RPE, and all others are secreted at the basal side
and back into the blood (Figure 15.3). It can be further argued that other ABC transporters known
also as multidrug resistance (MDR) proteins may be involved in efl ux of carotenoids and/or their
metabolites out of the retina. In humans, the three major types of MDR proteins include members
of the ABCB, ABCC, and ABCG subfamily, and they take part in the maintenance of the blood-
brain barrier (Sarkadi et al., 2006). MDR proteins act as efl ux transporters for a wide variety of
hydrophobic compounds. MDR1 (ABCB1/P-glycoprotein) is one of MDR proteins and is expressed
in the RPE (Aukunuru et al., 2001; Constable et al., 2006; Esser et al., 1998; Kennedy and Mangini,
2002). MDR1 transports amphipatic compounds with a molecular mass of 300-2000 Da including
anticancer drugs and antibiotics (Sarkadi et al., 2006) from cells. Studies on patients suffering from
proliferative vitreopathy show that MDR1 protein expression in the RPE is strongly upregulated
upon exposure to the drug used for its treatment, daunomycin (Esser et al., 1998).
Altogether, the role of transporters of lipophilic molecules regulating the movement of carotenoids
through the RPE and into the neural retina is another area awaiting experimental investigation.
SR-BI
POS
XBP
LP/Apo
Xan
SR-BII
Xan
Xan
Xan
LP/Apo
SR-BI
SR-BII
ABCA1
ABCA1
CD36
RPE
XBP
LP/Apo
Endosome
BCO
Xan
Vitamin A
LP
proA-car
CDP
Lyc
CD36
VLDLR
ABCA1
MDR
SR-BI
SR-BII
SR-BI
LDLR
SR-BII
Lyc
CDP
LDL
HDL
VLDL
XBP
VLDL
HDL
LDL
FIGURE 15.3
Hypothetical pathways responsible for carotenoid uptake, metabolic transformations, tran-
scytosis to the neural retin, or secretion to the blood.
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