What is the ultimate source of lipids feeding into BrM-LLP? It has long been expected that the daily ingestion of photoreceptor OS by RPE results in the export of material to BrM.
40 We postulated that a TG-rich apoB lipoprotein would be an excellent mechanism for releasing FA derived from PL in OS membranes. Current and previously published compositional data from BrM, LLP, and OS together provide little evidence for this initially attractive hypothesis. First, OS phagocytosis is not essential for neutral lipid secretion, based on experiments using FA supplementation of RPE cell lines.
12 Second, BrM-LLP are not TG-rich, shown in our study by LC-GC and TLC and previously by two other techniques.
6 13 Each method has strengths and limitations, but all data agree that the original report
16 of high TG mass in BrM/choroid cannot be replicated. (Our assays of BrM/choroid recovered 5.6- to 7.8-fold more total lipid, depending on assumptions, than reported in Ref.
16 ) Third, BrM-LLP are highly enriched in both EC,
7 absent from photoreceptors, and UC, sparse in the discs that constitute most OS membranes.
41 Fourth, the FA composition of neither the neutral lipids of the BrM-LLP core nor the PL of its surface resemble OS, particularly regarding the top three components: DHA, stearate, and palmitate.
42 We offer several explanations. First, OS lipids may be thoroughly catabolized by RPE before resynthesis as particle components. Second, DHA is efficiently recycled back to the retina,
43 leaving little for export. Third, OS-derived lipids may be present in a form (e.g., oxidized
44 ) not recognizable by our assays. Fourth, some lipid classes may be selectively and extensively hydrolyzed in the extracellular compartment after secretion (e.g., by choroid-resident
45 or RPE-secreted lipases), now a less likely option based on our analysis of whole choroid and RPE-J conditioned medium. Fifth, another input may dominate BrM-LLP, which compositionally resemble LDL more than they do OS, despite low linoleate levels. LDL taken up at RPE LDL receptors
46 47 can modify lysosomal acid lipase activity and can partition rapidly, within hours, into membranes of the neurosensory retina.
48 In this way, retina is unlike brain, which eschews plasma lipoprotein cholesterol and relies almost exclusively on endogenous synthesis.
49 Further, the ARPE-19 cell line can take up xanthophylls destined for macular pigment, normally transported in plasma on lipoproteins, via a basally expressed scavenger receptor.
50 Rather than disposing of OS, then, perhaps BrM-LLP dispose of the residual components of plasma lipoproteins after extracting specific nutrients.