Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

Progress in Retinal and Eye Research - Tập 28 - Trang 393-422 - 2009
Christine A. Curcio1, Mark Johnson2, Jiahn-Dar Huang3, Martin Rudolf4
1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA
2Biomedical Engineering Department, Northwestern University, Evanston, IL, USA
3National Eye Institute, National Institutes of Health, Bethesda, Md., USA
4University Eye Hospital Lübeck Universitätsklinikum Schleswig-Holstein, Lübeck, Germany

Tài liệu tham khảo

2001, 2001a. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS Report No. 8, Arch. Ophthalmol., 119, 1417, 10.1001/archopht.119.10.1417 2001, 2001b. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III), JAMA, 285, 2486, 10.1001/jama.285.19.2486 Adams, 1975, Lipid histochemistry, 100 Adiels, 2008, Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome, Arterioscler. Thromb. Vasc. Biol., 28, 1225, 10.1161/ATVBAHA.107.160192 Afshari, 2009, Improving RPE adhesion to Bruch's membrane, Eye, 10.1038/eye.2008.411 Alaupovic, 2003, The concept of apolipoprotein-defined lipoprotein families and its clinical significance, Curr. Atheroscler. Rep., 5, 459, 10.1007/s11883-003-0036-8 Anderson, 1989, A rapid method for staining large chylomicrons, J. Lipid Res., 30, 1819, 10.1016/S0022-2275(20)38212-2 Anderson, 2001, Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation, Am. J. Ophthalmol., 131, 767, 10.1016/S0002-9394(00)00961-2 Anderson, 2002, A role for local inflammation in the formation of drusen in the aging eye, Am. J. Ophthalmol., 134, 411, 10.1016/S0002-9394(02)01624-0 Anderson, 2004, Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration, Exp. Eye Res., 78, 243, 10.1016/j.exer.2003.10.011 Anderson, 2006, Drusenoid lesions and lipid-filled retinal pigment epithelium cells in a rhesus macula, Vet. Ophthalmol., 9, 201, 10.1111/j.1463-5224.2006.00463.x Athar, 2004, A simple, rapid, and sensitive fluorescence assay for microsomal triglyceride transfer protein, J. Lipid Res., 45, 764, 10.1194/jlr.D300026-JLR200 Bairaiti, 1963, The ultrastructure of the pigment epithelium and of the photoreceptor-pigment epithelium interface, J. Ultrastruct. Res., 9, 484, 10.1016/S0022-5320(63)80080-5 Ball, 1995, Evidence that the death of macrophage foam cells contributes to the lipid core of atheroma, Atherosclerosis, 114, 45, 10.1016/0021-9150(94)05463-S Bazan, 1990, Lipids in human lipofuscin-enriched subcellular fractions of two age population, Invest. Ophthalmol. Vis. Sci., 31, 1433 Bazan, 1992, Docosahexaenoic acid uptake and metabolism in photoreceptors: retinal conservation by an efficient retinal pigment epithelial cell-mediated recycling process, Adv. Exp. Med. Biol., 318, 295, 10.1007/978-1-4615-3426-6_26 Berriot-Varoqueaux, 2000, The role of the microsomal triglyceride transfer protein in abetalipoproteinemia, Annu. Rev. Nutr., 20, 663, 10.1146/annurev.nutr.20.1.663 Binder, 2007, Transplantation of the RPE in AMD, Prog. Retin. Eye Res., 26, 516, 10.1016/j.preteyeres.2007.02.002 Bird, 1986, Retinal pigment epithelial detachments in the elderly, Trans. Ophthalmol. Soc. UK, 105, 674 Björkegren, 2001, Lipoprotein secretion and triglyceride stores in the heart, J. Biol. Chem., 276, 38511, 10.1074/jbc.M106839200 Björkhem, 2004, Brain cholesterol: long secret life behind a barrier, Arterioscler Thromb. Vasc. Biol., 5, 5 Bocan, 1986, Ultrastructure of the human aortic fibrolipid lesion. Formation of the atherosclerotic lipid-rich core, Am. J. Pathol., 123, 413 Boesze-Battaglia, 1990, Relationship of cholesterol content to spatial distribution and age of disk membranes in retinal rod outer segments, J. Biol. Chem., 265, 18867, 10.1016/S0021-9258(17)30594-X Bressler, 1994, Clinicopathological correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration, Retina, 14, 130, 10.1097/00006982-199414020-00006 Bretillon, 2007, Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina, Curr. Eye Res., 32, 361, 10.1080/02713680701231857 Bretillon, 2008, ApoB100, LDLR-/- mice exhibit reduced electroretinographic response and cholesteryl esters deposits in the retina, Invest. Ophthalmol. Vis. Sci., 49, 1307, 10.1167/iovs.07-0808 Bretillon, 2008, Lipid and fatty acid profile of the retina, retinal pigment epithelium/choroid, and the lacrimal gland, and associations with adipose tissue fatty acids in human subjects, Exp. Eye Res., 87, 521, 10.1016/j.exer.2008.08.010 Broekhuyse, 1972, Lipids in tissues of the eye. VII. Changes in concentration and composition of sphingomyelins, cholesterol esters and other lipids in aging sclera, Biochim. Biophys. Acta, 280, 637, 10.1016/0005-2760(72)90143-9 Burtis, 1999 Camejo, 1998, Association of apo B lipoproteins with arterial proteoglycans: pathological significance and molecular basis, Atherosclerosis, 139, 205, 10.1016/S0021-9150(98)00107-5 Canter, 2008, Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration, PLoS One, 3, e2091, 10.1371/journal.pone.0002091 Casaroli-Marano, 1996, Lipoprotein lipase in highly vascularized structures of the eye, J. Lipid Res., 37, 1037, 10.1016/S0022-2275(20)42013-9 Cavelier, 2006, Lipid efflux by the ATP-binding cassette transporters ABCA1 and ABCG1, Biochim. Biophys. Acta, 1761, 655, 10.1016/j.bbalip.2006.04.012 Cerami, 1986, Role of nonenzymatic glycosylation in atherogenesis, J. Cell Biochem., 30, 111, 10.1002/jcb.240300203 Chang, 2001, Oxidized LDL bind to nonproteoglycan components of smooth muscle extracellular matrices, J. Lipid Res., 42, 824, 10.1016/S0022-2275(20)31645-X Chao, 1990, Characterization of two unique cholesterol-rich lipid particles isolated from human atherosclerotic lesions, Am. J. Pathol., 136, 169 Chen, 1992, Lipids of frog retinal pigment epithelium: comparison with rod outer segments, retina, plasma and red blood cells, Curr. Eye Res., 11, 793, 10.3109/02713689209000752 Chowers, 2001, Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients, Eye, 15, 525, 10.1038/eye.2001.167 Chuang, 1988, Bilaterality of tears of the retinal pigment epithelium, Br. J. Ophthalmol., 72, 918, 10.1136/bjo.72.12.918 Chung, 1994, Liposome-like particles isolated from human atherosclerotic plaques are structurally and compositionally similar to surface remnants of triglyceride-rich lipoproteins, Arterioscler Thromb., 14, 622, 10.1161/01.ATV.14.4.622 Chung, 2005, Phosphatidylcholine-rich acceptors, but not native HDL or its apolipoproteins, mobilize cholesterol from cholesterol-rich insoluble components of human atherosclerotic plaques, Biochem. Biophys. Acta Mol. Cell Biol. Lipids, 1733, 76 Chuo, 2007, Use of lipid-lowering agents for the prevention of age-related macular degeneration: a meta-analysis of observational studies, Ophthalmic Epidemiol., 14, 367, 10.1080/09286580701421684 Ciulla, 2009, Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration, Curr. Opin. Ophthalmol., 20, 158, 10.1097/ICU.0b013e32832d25b3 Congdon, 2004, Causes and prevalence of visual impairment among adults in the United States, Arch. Ophthalmol., 122, 477, 10.1001/archopht.122.4.477 Connor, 2007, The prime role of HDL to transport lutein into the retina: evidence from HDL-deficient WHAM chicks having a mutant ABCA1 transporter, Invest. Ophthalmol. Vis. Sci., 48, 4226, 10.1167/iovs.06-1275 Contois, 2009, Apolipoprotein B and cardiovascular disease risk: position statement from the AACC lipoproteins and vascular diseases Division working group on best Practices, Clin. Chem., 55, 407, 10.1373/clinchem.2008.118356 Cousins, 2002, The role of aging, high fat diet and blue light exposure in an experimental mouse model for basal laminar deposit formation, Exp. Eye Res., 75, 543, 10.1006/exer.2002.2047 Crabb, 2002, Drusen proteome analysis: an approach to the etiology of age-related macular degeneration, Proc. Natl. Acad. Sci. U S A, 99, 14682, 10.1073/pnas.222551899 Crispin, 2002, Ocular lipid deposition and hyperlipoproteinaemia, Prog. Retin. Eye Res., 21, 169, 10.1016/S1350-9462(02)00004-6 Cullen, 1998, Phenotype-dependent differences in apolipoprotein E metabolism and cholesterol homeostasis in human monocyte-derived macrophages, J. Clin. Invest., 101, 1670, 10.1172/JCI119887 Curcio, 2005, Imaging maculopathy in the post-mortem human retina, Vis. Res., 45, 3496, 10.1016/j.visres.2005.07.038 Curcio, 1998, The Alabama age-related macular degeneration grading system for donor eyes, Invest. Ophthalmol. Vis. Sci., 39, 1085 Curcio, 2000, Peripapillary chorioretinal atrophy: bruch's membrane changes and photoreceptor loss, Ophthalmology, 107, 334, 10.1016/S0161-6420(99)00037-8 Curcio, 2001, Accumulation of cholesterol with age in human Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 42, 265 Curcio, 2005, Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy, Exp. Eye Res., 81, 731, 10.1016/j.exer.2005.04.012 Curcio, 2005, Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles, Exp. Eye Res., 80, 761, 10.1016/j.exer.2004.09.017 Curcio, 1999, Basal linear deposit and large drusen are specific for early age-related maculopathy, Arch. Ophthalmol., 117, 329, 10.1001/archopht.117.3.329 Dashti, 2006, Plasma apolipoproteins and risk for age-related maculopathy, Br. J. Ophthalmol., 90, 1028, 10.1136/bjo.2006.093856 Davies, 1996, Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995, Circulation, 94, 2013, 10.1161/01.CIR.94.8.2013 Davis, 2005, The age-related eye disease study severity scale for age-related macular degeneration: AREDS report No. 17, Arch. Ophthalmol., 123, 1484, 10.1001/archopht.123.11.1484 Del Priore, 2002, Age-related changes in human RPE cell density and apoptosis proportion in situ, Invest. Ophthalmol. Vis. Sci., 43, 3312 Del Priore, 1998, Reattachment rate of human retinal pigment epithelium to layers of human Bruch's membrane, Arch. Ophthalmol., 116, 335, 10.1001/archopht.116.3.335 Dewan, 2006, HTRA1 promoter polymorphism in wet age-related macular degeneration, Science, 314, 989, 10.1126/science.1133807 Dithmar, 2000, Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice, Invest. Ophthalmol. Vis. Sci., 41, 2035 Dougan, 2007, MTP regulated by an alternate promoter is essential for NKT cell development, J. Exp. Med., 204, 533, 10.1084/jem.20062006 Duncan, 2002, Human retinal pigment epithelial cells express scavenger receptors BI and BII, Biochem. Biophys. Res. Commun., 292, 1017, 10.1006/bbrc.2002.6756 During, 2008, Xanthophylls are preferentially taken up compared to beta -carotene by retinal cells via a scavenger receptor BI-dependent mechanism, J. Lipid Res., 49, 1715, 10.1194/jlr.M700580-JLR200 Eckhart, 2000, Melanin binds reversibly to thermostable DNA polymerase and inhibits its activity, Biochem. Biophys. Res. Commun., 271, 726, 10.1006/bbrc.2000.2716 Edwards, 2007, Molecular genetics of AMD and current animal models, Angiogenesis, 10, 119, 10.1007/s10456-007-9064-2 El Baba, 1986, Clinicopathologic correlation of lipidization and detachment of the retinal pigment epithelium, Am. J. Ophthalmol., 101, 576, 10.1016/0002-9394(86)90948-7 Eldred, 1993, Retinal age pigments generated by self-assembling lysosomotropic detergents, Nature, 361, 724, 10.1038/361724a0 Elner, 2002, Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids, Trans. Am. Ophthalmol. Soc., 100, 301 Espinosa-Heidmann, 2004, Basal laminar deposit formation in APO B100 transgenic mice: complex interactions between dietary fat, blue light, and vitamin E, Invest. Ophthalmol. Vis. Sci., 45, 260, 10.1167/iovs.03-0910 Ethier, 2004, Ocular biomechanics and biotransport, Annu. Rev. Biomed. Eng., 6, 249, 10.1146/annurev.bioeng.6.040803.140055 Farese, 1995, Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes, Proc. Natl. Acad. Sci. U S A, 92, 1774, 10.1073/pnas.92.5.1774 Fariss, 1997, Tissue inhibitor of metalloproteinases-3 is a component of Bruch's membrane of the eye, Am. J. Pathol., 150, 323 Feeney-Burns, 1985, Age-related changes in the ultrastructure of Bruch's membrane, Am. J. Ophthalmol., 100, 686, 10.1016/0002-9394(85)90625-7 Feeney-Burns, 1981, Maculopathy in cynomologus monkeys. A correlated fluorescein angiographic and ultrastructural study, Arch. Ophthalmol., 99, 664, 10.1001/archopht.1981.03930010664013 Fijalkowski, 2009, Transgenic mice that express human apolipoprotein B100 (ApoB100) in the retinal pigmented epithelium (RPE) and liver Develop phenotypic features of early age-related macular degeneration (AMD), Invest. Ophthalmol. Vis. Sci., 50, e774 Fine, 1978, Pigment epithelial windows and drusen: an animal model, Invest. Ophthalmol. Vis. Sci., 17, 1059 Finnemann, 2002, The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium, Proc. Natl. Acad. Sci. U S A, 99, 3842, 10.1073/pnas.052025899 Fisher, 2002, Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins, J. Biol. Chem., 277, 17377, 10.1074/jbc.R100068200 Fliesler, 1983, Chemistry and metabolism of lipids in the vertebrate retina, Progr Lipid Res., 22, 79, 10.1016/0163-7827(83)90004-8 Fliesler, 1997, Isoprenoid metabolism in the vertebrate retina, Int. J. Biochem. Cell Biol., 29, 877, 10.1016/S1357-2725(97)00018-6 Forte, 1986, Electron microscopy of negatively stained lipoproteins, Methods Enzymol., 128, 442, 10.1016/0076-6879(86)28086-6 Frank, 1989, Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freeze-etching, J. Lipid Res., 30, 967, 10.1016/S0022-2275(20)38299-7 Friedman, 2004, Update of the vascular model of AMD, Br. J. Ophthalmol., 88, 161, 10.1136/bjo.2003.036277 Friedrichson, 1995, Vitamin E in macular and peripheral tissues of the human eye, Curr. Eye Res., 14, 693, 10.3109/02713689508998497 Fujihara, 2009, A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD, Exp. Eye Res., 88, 1115, 10.1016/j.exer.2009.01.017 Gaynor, 1996, Cholesterol accumulation in human cornea: evidence that extracellular cholesteryl ester-rich lipid particles deposit independently of foam cells, J. Lipid Res., 37, 1849, 10.1016/S0022-2275(20)37550-7 Giambernardi, 1998, Bovine serum albumin reverses inhibition of RT-PCR by melanin, Biotechniques, 25, 564, 10.2144/98254bm03 Gold, 2006, Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration, Nat. Genet., 38, 458, 10.1038/ng1750 Goldberg, 2009, Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways, J. Lipid Res., 10.1194/jlr.R800085-JLR200 Gonzalez-Fernandez, 2008, Focus on Molecules: interphotoreceptor retinoid-binding protein (IRBP), Exp. Eye Res., 86, 169, 10.1016/j.exer.2006.09.003 Gordiyenko, 2004, RPE cells internalize low-density lipoprotein (LDL) and oxidized LDL (oxLDL) in large quantities in vitro and in vivo, Invest. Ophthalmol. Vis. Sci., 45, 2822, 10.1167/iovs.04-0074 Gordon, 1994, Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability, Proc. Natl. Acad. Sci. U S A, 91, 7628, 10.1073/pnas.91.16.7628 Gordon, 2000, Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly, Biochim. Biophys. Acta, 1486, 72, 10.1016/S1388-1981(00)00049-4 Grant, 2001, Treatable forms of retinitis pigmentosa associated with systemic neurological disorders, Int. Ophthalmol. Clin., 41, 103, 10.1097/00004397-200101000-00010 Green, 1993, Age-related macular degeneration histopathologic studies: the 1992 Lorenz E. Zimmerman Lecture, Ophthalmology, 100, 1519, 10.1016/S0161-6420(93)31466-1 Grindle, 1978, Ageing changes in Bruch's membrane and their functional implications, Trans. Ophthalmol. Soc. U K, 98, 172 Grisanti, 2008, The role of vascular endothelial growth factor and other endogenous interplayers in age-related macular degeneration, Prog. Retin. Eye Res., 27, 372, 10.1016/j.preteyeres.2008.05.002 Grossniklaus, 2004, Choroidal neovascularization, Am. J. Ophthalmol., 137, 496, 10.1016/j.ajo.2003.09.042 Gülcan, 1993, Lipids of human retina, retinal pigment epithelium, and Bruch's membrane/choroid: comparison of macular and peripheral regions, Invest. Ophthalmol. Vis. Sci., 34, 3187 Gullapalli, 2008, Culture-induced increase in alpha integrin subunit expression in retinal pigment epithelium is important for improved resurfacing of aged human Bruch's membrane, Exp. Eye Res., 86, 189, 10.1016/j.exer.2007.10.009 Guyton, 1985, Quantitative ultrastructural analysis of perifibrous lipid and its association with elastin in nonatherosclerotic human aorta, Arteriosclerosis, 5, 644, 10.1161/01.ATV.5.6.644 Guyton, 1988, Ultrastructural discrimination of lipid droplets and vesicles in atherosclerosis: value of osmium-thiocarbohydrazide-osmium and tannic acid-paraphenylenediamine techniques, J. Histochem. Cytochem., 36, 1319, 10.1177/36.10.2458408 Guyton, 1989, The lipid-rich core region of human atherosclerotic fibrous plaques. Prevalence of small lipid droplets and vesicles by electron microscopy, Am. J. Pathol., 134, 705 Guyton, 1993, Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic fatty streaks, Am. J. Pathol., 143, 1444 Guyton, 1996, Development of the lipid-rich core in human atherosclerosis, Arterioscler Thromb., 16, 4, 10.1161/01.ATV.16.1.4 Hacquebard, 2005, Vitamin E: absorption, plasma transport and cell uptake, Curr. Opin. Clin. Nutr. Metab. Care, 8, 133, 10.1097/00075197-200503000-00005 Hageman, 1999, Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells, FASEB J., 13, 477, 10.1096/fasebj.13.3.477 Hageman, 2001, An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration, Progr Ret Eye Res., 20, 705, 10.1016/S1350-9462(01)00010-6 Hageman, 2005, A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration, Proc. Natl. Acad. Sci. U S A, 102, 7227, 10.1073/pnas.0501536102 Haimovici, 2001, The lipid composition of drusen, Bruch's membrane, and sclera by hot stage polarizing microscopy, Invest. Ophthalmol. Vis. Sci., 42, 1592 Handa, 2007, New molecular histopathologic insights into the pathogenesis of age-related macular degeneration, Int. Ophthalmol. Clin., 47, 15, 10.1097/IIO.0b013e31802bd546 Handa, 1999, Increase in the advanced glycation end product pentosidine in Bruch's membrane with age, Invest. Ophthalmol. Vis. Sci., 40, 775 Hatters, 2006, Apolipoprotein E structure: insights into function, Trends Biochem. Sci., 31, 445, 10.1016/j.tibs.2006.06.008 Havel, 2001, Introduction: structure and metabolism of plasma lipoproteins, 2707 Hayes, 1989, Retinal pigment epithelium possesses both LDL and scavenger receptor activity, Invest. Ophthalmol. Vis. Sci., 30, 225 Hayward, 2003, Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration, Hum. Mol. Genet., 12, 2657, 10.1093/hmg/ddg289 Hewitt, 1989, Analysis of newly synthesized Bruch's membrane proteoglycans, Invest. Ophthalmol. Vis. Sci., 30, 478 Hillenkamp, 2004, Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina, Invest. Ophthalmol. Vis. Sci., 45, 4529, 10.1167/iovs.04-0919 Hirosawa, K., Yamada, E. (1976). Localization of vitamin A in the mouse retina as revealed by autoradiography. Paper presented at: The structure of the Eye, Third Symposium (Tokyo, Japanese Journal of Ophthalmology). Hogan, 1972, Role of the retinal pigment epithelium in macular disease, Trans. Am. Acad. Ophthalmol. Otolaryngol., 76, 64 Hogan, 1971 Holm, 1999, Hormone-sensitive lipase and neutral cholesteryl ester lipase, Methods Mol. Biol., 109, 109 Holz, 1994, Analysis of lipid deposits extracted from human macular and peripheral Bruch's membrane, Arch. Ophthalmol., 112, 402, 10.1001/archopht.1994.01090150132035 Huang, 2007, Lipid accumulation Huang, 2007, Lipoprotein-like particles represent a major portion of lipids found in human macular Bruch's membrane (BrM), Invest. Ophthalmol. Vis. Sci. Huang, 2007, Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch, Exp. Eye Res., 85, 202, 10.1016/j.exer.2007.03.011 Huang, 2008, Morphometric analysis of lipoprotein-like particle accumulation in aging human macular Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 49, 2721, 10.1167/iovs.07-1196 Huang, 2008, Perfusion of low-density lipoprotein through Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 49 Huang, J.-D., Kruth, H.S., Johnson, M., 2009. Transport of low-density lipoproteins through Bruch's membrane and choroid. under review. Hussain, 2002, Age-related alterations in the diffusional transport of amino acids across the human Bruch's-choroid complex, J. Opt. Soc. Am. A, 19, 166, 10.1364/JOSAA.19.000166 Hussain, 2003, Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly, J. Lipid Res., 44, 22, 10.1194/jlr.R200014-JLR200 Hussain, 2008, Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism, Curr. Opin. Lipidol., 19, 277, 10.1097/MOL.0b013e3282feea85 Iglesias, 1996, Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids, Clin. Chim. Acta, 248, 157, 10.1016/0009-8981(95)06251-3 Iqbal, 2003, Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells, J. Biol. Chem., 278, 31610, 10.1074/jbc.M301177200 Ishibashi, 1986, Formation of drusen in the human eye, Am. J. Ophthalmol., 101, 342, 10.1016/0002-9394(86)90830-5 Ishibashi, 1986, Pathogenesis of drusen in the primate, Invest. Ophthalm Vis. Sci., 27, 184 Ishida, 2004, Regulated expression of apolipoprotein E by human retinal pigment epithelial cells, J. Lipid Res., 45, 263, 10.1194/jlr.M300306-JLR200 Ishida, 2006, High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture, Br. J. Ophthalmol., 90, 616, 10.1136/bjo.2005.085076 Jackson, 2005, Photoreceptor degeneration in aging and age-related maculopathy, 45 Jamil, 1995, Microsomal triglyceride transfer protein. Specificity of lipid binding and transport, J. Biol. Chem., 270, 6549, 10.1074/jbc.270.12.6549 Javitt, 2008, Oxysterols: novel biologic roles for the 21st century, Steroids, 73, 149, 10.1016/j.steroids.2007.10.004 Joffre, 2007, Oxysterols induced inflammation and oxidation in primary porcine retinal pigment epithelial cells, Curr. Eye Res., 32, 271, 10.1080/02713680601187951 Johnson, 2000, A potential role for immune complex pathogenesis in drusen formation, Exp. Eye Res., 70, 441, 10.1006/exer.1999.0798 Johnson, 2001, Complement activation and inflammatory processes in drusen formation and age related macular degeneration, Exp. Eye Res., 73, 887, 10.1006/exer.2001.1094 Johnson, 2002, The Alzheimer's A{beta}-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration, Proc. Natl. Acad. Sci. U S A, 99, 11830, 10.1073/pnas.192203399 Johnson, 2007, Comparison of morphology of human macular and peripheral Bruch's membrane in older eyes, Curr. Eye Res., 32, 791, 10.1080/02713680701550660 Jonas, 2002, Lipoprotein structure, 483 Kamei, 2007, Scavenger receptors for oxidized lipoprotein in age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 48, 1801, 10.1167/iovs.06-0699 Kamei, 1999, TIMP-3 in Bruch's membrane: changes during aging and in age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 40, 2367 Kanda, 2007, A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration, Proc. Natl. Acad. Sci. U S A, 104, 16227, 10.1073/pnas.0703933104 Karwatowski, 1995, Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens, Br. J. Ophthalmol., 79, 944, 10.1136/bjo.79.10.944 Katz, 1980, Isolation and partial characterization of the lipid phases of human atherosclerotic plaques, J. Biol. Chem., 255, 10.1016/S0021-9258(18)43457-6 Kaur, 2008, Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management, Prog. Retin. Eye Res., 27, 622, 10.1016/j.preteyeres.2008.09.003 Khanifar, 2008, Drusen ultrastructure imaging with spectral domain optical coherence tomography in age-related macular degeneration, Ophthalmology, 115, 1883, 10.1016/j.ophtha.2008.04.041 Killingsworth, 1987, Age-related components of Bruch's membrane, Graefes Arch. Clin. Exp. Ophthalmol., 225, 406, 10.1007/BF02334166 Klaver, 1998, Genetic association of apolipoprotein E with age-related macular degeneration, Am. J. Hum. Genet., 63, 200, 10.1086/301901 Klein, 1991, The Wisconsin age-related maculopathy grading system, Ophthalmol, 98, 1128, 10.1016/S0161-6420(91)32186-9 Klein, 2004, The epidemiology of age-related macular degeneration, Am. J. Ophthalmol., 137, 486, 10.1016/j.ajo.2003.11.069 Klein, 2007, Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study, Ophthalmology, 114, 253, 10.1016/j.ophtha.2006.10.040 Kliffen, 1996, Identification of glycosaminoglycans in age-related macular deposits, Arch. Ophthalmol., 114, 1009, 10.1001/archopht.1996.01100140217021 Kliffen, 2000, The APO*E3-Leiden mouse as an animal model for basal laminar deposit, Br. J. Ophthalmol., 84, 1415, 10.1136/bjo.84.12.1415 Knupp, 2000, Structure of abnormal molecular assemblies (collagen VI) associated with human full thickness macular holes, J. Struct. Biol., 129, 38, 10.1006/jsbi.1999.4202 Kouchi, 2006, Ocular lesions in Watanabe heritable hyperlipidemic rabbits, Vet. Ophthalmol., 9, 145, 10.1111/j.1463-5224.2006.00453.x Kovanen, 1999, Decorin links low-density lipoproteins (LDL) to collagen: a novel mechanism for retention of LDL in the atherosclerotic plaque, Trends Cardiovasc. Med., 9, 86, 10.1016/S1050-1738(99)00013-4 Kruth, 1984, Histochemical detection of esterified cholesterol within human atherosclerotic lesions using the fluorescent probe filipin, Atherosclerosis, 51, 281, 10.1016/0021-9150(84)90175-8 Kruth, 1984, Localization of unesterified cholesterol in human atherosclerotic lesions. Demonstration of filipin-positive, oil red O-negative particles, Am. J. Pathol., 114, 201 Kruth, 1997, The fate of lipoprotein cholesterol entering the arterial wall, Curr. Opin. Lipidol., 8, 246, 10.1097/00041433-199710000-00002 Kuntz, 1996, Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration, Invest. Ophthalmol. Vis. Sci., 37, 1772 Lakkaraju, 2007, The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells, Proc. Natl. Acad. Sci. U S A, 104, 11026, 10.1073/pnas.0702504104 Lakkaraju, 2008, Itinerant exosomes: emerging roles in cell and tissue polarity, Trends Cell Biol., 18, 199, 10.1016/j.tcb.2008.03.002 Lauber, 1924, The origin of hyaline formations within the eye, Ber Ü D Deutsch Ophth Gesellsch, 44 Le, 2008, Inducible expression of cre recombinase in the retinal pigmented epithelium, Invest. Ophthalmol. Vis. Sci., 49, 1248, 10.1167/iovs.07-1105 Lee, 2006, Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina, Exp. Eye Res., 83, 465, 10.1016/j.exer.2005.11.018 Leiper, 1994, Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells, J. Biol. Chem., 269, 21951, 10.1016/S0021-9258(17)31740-4 Lengyel, 2007, High concentration of zinc in sub-retinal pigment epithelial deposits, Exp. Eye Res., 84, 772, 10.1016/j.exer.2006.12.015 Li, 2005, Lipoprotein-like particles and cholesteryl esters in human Bruch's membrane: initial characterization, Invest. Ophthalmol. Vis. Sci., 46, 2576, 10.1167/iovs.05-0034 Li, 2005, Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy, J. Lipid Res., 46, 628, 10.1194/jlr.M400428-JLR200 Li, 2006, Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression, Invest. Ophthalmol. Vis. Sci., 47, 3119, 10.1167/iovs.05-1446 Li, 2007, Distribution and composition of esterified and unesterified cholesterol in extra-macular drusen, Exp. Eye Res., 85, 192, 10.1016/j.exer.2007.04.002 Lin, 2007, Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane, Mol. Vis., 13, 1203 Loane, 2008, Transport and retinal capture of lutein and zeaxanthin with reference to age-related macular degeneration, Surv. Ophthalmol., 53, 68, 10.1016/j.survophthal.2007.10.008 Löffler, 1986, Basal linear deposit in the human macula, Graefes Arch. Clin. Exp. Ophthalmol., 224, 493, 10.1007/BF02154735 Lommatzsch, 2008, Are low inflammatory reactions involved in exudative age-related macular degeneration? Morphological and immunhistochemical analysis of AMD associated with basal deposits, Graefes Arch. Clin. Exp. Ophthalmol., 246, 803, 10.1007/s00417-007-0749-4 Luibl, 2006, Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers, J. Clin. Invest., 116, 378, 10.1172/JCI25843 Luna, 1968 Lusis, 2004, Genetic basis of atherosclerosis: part I: new genes and pathways, Circulation, 110, 1868, 10.1161/01.CIR.0000143041.58692.CC Madsen, 2004, Human placenta secretes apolipoprotein B-100-containing lipoproteins, J. Biol. Chem., 279, 55271, 10.1074/jbc.M411404200 Majji, 2000, Age-related retinal pigment epithelium and Bruch's membrane degeneration in senescence-accelerated mouse, Invest. Ophthalmol. Vis. Sci., 41, 3936 Malek, 1999, Hemodynamic shear stress and its role in atherosclerosis, Jama, 282, 2035, 10.1001/jama.282.21.2035 Malek, 2003, Apolipoprotein B in cholesterol-containing drusen and basal deposits in eyes with age-related maculopathy, Am. J. Pathol., 162, 413, 10.1016/S0002-9440(10)63836-9 Malek, 2005, Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration, Proc. Natl. Acad. Sci. U S A, 102, 11900, 10.1073/pnas.0503015102 Maminishkis, 2006, Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue, Invest. Ophthalmol. Vis. Sci., 47, 3612, 10.1167/iovs.05-1622 Marshall, 1992, Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula, Br. J. Ophthalmol., 76, 607, 10.1136/bjo.76.10.607 Marshall, 1998, Aging and Bruch's membrane, 669 McCarty, 2008, Effects of particulates and lipids on the hydraulic conductivity of Matrigel, J. Appl. Physiol., 105, 621, 10.1152/japplphysiol.01245.2007 Messinger, 2009, Transition from Lipid Wall to basal linear deposit In age-related maculopathy (ARM), Invest. Ophthalmol. Vis. Sci. Miceli, 2000, Pathologic changes in the retinal pigment epithelium and Bruch's membrane of fat-fed atherogenic mice, Curr. Eye Res., 20, 8, 10.1076/0271-3683(200001)2011-HFT008 Milam, 2000, Dominant late-onset retinal degeneration with regional variation of sub-RPE deposits, retinal function, and photoreceptor degeneration, Ophthalmology, 107, 2256, 10.1016/S0161-6420(00)00419-X Moghadasian, 2002, Experimental atherosclerosis: a historical overview, Life Sci., 70, 855, 10.1016/S0024-3205(01)01479-5 Mohler, 2007, Identification of a novel isoform of microsomal triglyceride transfer protein, J. Biol. Chem., 282, 26981, 10.1074/jbc.M700500200 Montezuma, 2007, Review of genetics in age related macular degeneration, Semin. Ophthalmol., 22, 229, 10.1080/08820530701745140 Moore, 2001, The effect of age on the macromolecular permeability of human Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 42, 2970 Moore, 1995, Age-related variation in the hydraulic conductivity of Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 36, 1290 Moreira, 2009, 7-Ketocholesterol is present in lipid deposits in the primate retina: potential implication in the induction of VEGF and CNV formation, Invest. Ophthalmol. Vis. Sci., 50, 523, 10.1167/iovs.08-2373 Mori, 2002, Site-specific somatic mutagenesis in the retinal pigment epithelium, Invest. Ophthalmol. Vis. Sci., 43, 1384 Mullins, 2000, Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease, FASEB J., 14, 835, 10.1096/fasebj.14.7.835 Mullins, 1999, Human ocular drusen possess novel core domains with a distinct carbohydrate composition, J. Histochem. Cytochem., 47, 1533, 10.1177/002215549904701205 Nakaisumi, 1964, The ultrastructure of Bruch's membrane. III. The macular area of the human eye, Arch. Ophthalmol., 72, 395, 10.1001/archopht.1964.00970020395018 Newsome, 1987, Detection of specific extracellular matrix molecules in drusen, Bruch's membrane, and ciliary body, Am. J. Ophthalmol., 104, 373, 10.1016/0002-9394(87)90227-3 Nickle, 2007, The opsins of the vertebrate retina: insights from structural, biochemical, and evolutionary studies, Cell Mol. Life Sci., 64, 2917, 10.1007/s00018-007-7253-1 Nielsen, 1998, Genes for apolipoprotein B and microsomal triglyceride transfer protein are expressed in the heart: evidence that the heart has the capacity to synthesize and secrete lipoproteins, Circulation, 98, 13, 10.1161/01.CIR.98.1.13 Nievelstein, 1991, Lipid accumulation in rabbit aortic intima 2 hours after bolus infusion of low density lipoprotein. A deep-etch and immunolocalization study of ultrarapidly frozen tissue, Arterioscler Thromb., 11, 1795, 10.1161/01.ATV.11.6.1795 Nussenblatt, 2007, Age-related macular degeneration and the immune response: implications for therapy, Am. J. Ophthalmol., 144, 618, 10.1016/j.ajo.2007.06.025 O'Brien, 2004, Smooth muscle cell biglycan overexpression results in increased lipoprotein retention on extracellular matrix: implications for the retention of lipoproteins in atherosclerosis, Atherosclerosis, 177, 29, 10.1016/j.atherosclerosis.2004.07.007 Oksjoki, 2007, Function and regulation of the complement system in cardiovascular diseases, Front. Biosci., 12, 4696, 10.2741/2419 Olofsson, 2005, Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis, J. Intern. Med., 258, 395, 10.1111/j.1365-2796.2005.01556.x Ong, 2001, Effects of cholesterol and apolipoprotein E on retinal abnormalities in apoE-deficient mice, Invest. Ophthalmol. Vis. Sci., 42, 1891 Ong, 2003, Oxysterol-induced toxicity in R28 and ARPE-19 cells, Neurochem. Res., 28, 883, 10.1023/A:1023223409798 Pauleikhoff, 1990, Aging changes in Bruch's membrane: a histochemical and morphological study, Ophthalmology, 97, 171, 10.1016/S0161-6420(90)32619-2 Pauleikhoff, 1992, Correlation between biochemical composition and fluorescein binding of deposits in Bruch's membrane, Ophthalmol, 99, 1548, 10.1016/S0161-6420(92)31768-3 Pauleikhoff, 1994, Biochemical and histochemical analysis of age related lipid deposits in Bruch's membrane, Ophthalmologe, 91, 730 Pauleikhoff, 2000, Adhesive properties of basal membranes of Bruch's membrane. Immunohistochemical studies of age-dependent changes in adhesive molecules and lipid deposits, Ophthalmologe, 97, 243, 10.1007/s003470050520 Pentikainen, 1997, Human arterial proteoglycans increase the rate of proteolytic fusion of low density lipoprotein particles, J. Biol. Chem., 272, 25283, 10.1074/jbc.272.40.25283 Pentikainen, 2000, Lipoprotein lipase (LPL) strongly links native and oxidized low density lipoprotein particles to decorin-coated collagen. Roles for both dimeric and monomeric forms of LPL, J. Biol. Chem., 275, 5694, 10.1074/jbc.275.8.5694 Pentikainen, 2002, Lipoprotein lipase in the arterial wall - Linking LDL to the arterial extracellular matrix and much more, Arteriosclerosis Thromb. Vasc. Biol., 22, 211, 10.1161/hq0102.101551 Qtaishat, 2003, Acute radiolabeling of retinoids in eye tissues of normal and rpe65-deficient mice, Invest. Ophthalmol. Vis. Sci., 44, 1435, 10.1167/iovs.02-0679 Raabe, 1998, Knockout of the abetalipoproteinemia gene in mice: reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes, Proc. Natl. Acad. Sci. U S A, 95, 8686, 10.1073/pnas.95.15.8686 Ramírez, 2006, Macroglial and retinal changes in hypercholesterolemic rabbits after normalization of cholesterol levels, Exp. Eye Res., 83, 1423, 10.1016/j.exer.2006.07.023 Ramrattan, 1994, Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging, Invest. Ophthalmol. Vis. Sci., 35, 2857 Raoul, 2008, Lipid-bloated subretinal microglial cells are at the origin of drusen appearance in CX3CR1-deficient mice, Ophthalmic Res., 40, 115, 10.1159/000119860 Rapp, 1994, Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque, Arterioscler Thromb., 14, 1767, 10.1161/01.ATV.14.11.1767 Rapp, 2000, Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina, Invest. Ophthalmol. Vis. Sci., 41, 1200 Reale, 2008, New components of ‘basal laminar deposits’ in age-related macular degeneration, Cells Tissues Organs Redmond, 1998, Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle, Nat. Genet., 20, 344, 10.1038/3813 Richards, 2007, Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory statesthe examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration, Adv. Immunol., 96, 141, 10.1016/S0065-2776(07)96004-6 Ridker, 2002, Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events, N. Engl. J. Med., 347, 1557, 10.1056/NEJMoa021993 Rittmann, 2007, Engineering away lysosomal junk: medical bioremediation, Rejuvenation Res., 10, 359, 10.1089/rej.2007.0594 Robison, 1977, Vitamin A storage and peroxisomes in retinal pigment epithelium and liver, Invest. Ophthalmol. Vis. Sci., 16, 1110 Rodriguez, 2004, Cytotoxicity of oxidized low-density lipoprotein in cultured RPE cells is dependent on the formation of 7-ketocholesterol, Invest. Ophthalmol. Vis. Sci., 45, 2830, 10.1167/iovs.04-0075 Rodriguez de Turco, 1999, Selective retinal pigment epithelial cell lipid metabolism and remodeling conserves photoreceptor docosahexaenoic acid following phagocytosis, J. Neurosci. Res., 57, 479, 10.1002/(SICI)1097-4547(19990815)57:4<479::AID-JNR7>3.0.CO;2-U Rones, 1937, Formation of drusen of the lamina vitrea, Arch. Ophthalmol., 18, 288, 10.1001/archopht.1937.00850090056007 Ruberg, 2006, Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton MRS, J. Lipid Res., 47, 310, 10.1194/jlr.M500431-JLR200 Ruberti, 2003, Quick-freeze/deep-etch visualization of age-related lipid accumulation in Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 44, 1753, 10.1167/iovs.02-0496 Rudolf, 2005, Increased expression of vascular endothelial growth factor associated with accumulation of lipids in Bruch's membrane of LDL receptor knockout mice, Br. J. Ophthalmol., 89, 1627, 10.1136/bjo.2005.071183 Rudolf, 2008, Prevalence and morphology of druse types in the macula and periphery of eyes with age-related maculopathy, Invest. Ophthalmol. Vis. Sci., 49, 1200, 10.1167/iovs.07-1466 Rudolf, 2008, Sub-retinal drusenoid deposits in human retina: organization and composition, Exp. Eye Res., 87, 402, 10.1016/j.exer.2008.07.010 Ruiz, 1996, TIMP-3 is expressed in the human retinal pigment epithelium, Biochem. Biophys. Res. Commun., 226, 467, 10.1006/bbrc.1996.1379 Ryeom, 1996, Binding of anionic phospholipids to retinal pigment epithelium may be mediated by the scavenger receptor CD36, J. Biol. Chem., 271, 20536, 10.1074/jbc.271.34.20536 Sadaba, 2008, Antioxidant effects of vitamins C and E, multivitamin-mineral complex and flavonoids in a model of retinal oxidative stress: the ApoE-deficient mouse, Exp. Eye Res., 86, 470, 10.1016/j.exer.2007.11.020 Salazar, 2007, Alterations in the choroid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol levels, Exp. Eye Res., 84, 412, 10.1016/j.exer.2006.10.012 Sallo, 2009, Bruch's membrane changes in transgenic mice overexpressing the human biglycan and apolipoprotein b-100 genes, Exp. Eye Res., 10.1016/j.exer.2009.03.006 Sarks, 1976, Ageing and degeneration in the macular region: a clinico-pathological study, Br. J. Ophthalmol., 60, 324, 10.1136/bjo.60.5.324 Sarks, 1980, Council Lecture: drusen and their relationship to senile macular degeneration, Aust. J. Ophthalmol., 8, 117, 10.1111/j.1442-9071.1980.tb01670.x Sarks, 1980, Softening of drusen and subretinal neovascularization, Trans. Ophthalmol. Soc. U K, 100, 414 Sarks, 1988, Evolution of geographic atrophy of the retinal pigment epithelium, Eye, 2, 552, 10.1038/eye.1988.106 Sarks, 1999, Early drusen formation in the normal and aging eye and their relation to age-related maculopathy: a clinicopathological study, Br. J. Ophthalmol., 83, 358, 10.1136/bjo.83.3.358 Sarks, 2007, Relationship of basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 48, 968, 10.1167/iovs.06-0443 Schmidt-Erfurth, 2008, Ultrastructural changes in a murine model of graded Bruch membrane lipoidal degeneration and corresponding VEGF164 detection, Invest. Ophthalmol. Vis. Sci., 49, 390, 10.1167/IOVS.07-0227 Schonfeld, 2003, Familial hypobetalipoproteinemia: a review, J. Lipid Res., 44, 878, 10.1194/jlr.R300002-JLR200 Schwenke, 1989, Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I. Focal increases in arterial LDL concentration precede development of fatty streak lesions, Arteriosclerosis, 9 Schwenke, 1989, Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries, Arteriosclerosis, 9, 908, 10.1161/01.ATV.9.6.908 Scott, 1989, Membrane docosohexanoate is supplied to the developing brain and retina by the liver, Proc. Natl. Acad. Sci., 86, 2903, 10.1073/pnas.86.8.2903 Segrest, 1999, N-terminal domain of apolipoprotein B has structural homology to lipovitellin and microsomal triglyceride transfer protein: a “lipid pocket” model for self-assembly of apob-containing lipoprotein particles, J. Lipid Res., 40, 1401, 10.1016/S0022-2275(20)33382-4 Seifert, 1989, Prelesional complement activation in experimental atherosclerosis. Terminal C5b-9 complement deposition coincides with cholesterol accumulation in the aortic intima of hypercholesterolemic rabbits, Lab. Invest., 60, 747 Selkoe, 1982, Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea, Science, 215, 1243, 10.1126/science.6120571 Sellers, 2001, Lipoprotein assembly capacity of the mammary tumor-derived cell line C127 is due to the expression of functional microsomal triglyceride transfer protein, J. Lipid Res., 42, 1897, 10.1016/S0022-2275(20)31516-9 Seth, 2008, Complement-associated deposits in the human retina, Invest. Ophthalmol. Vis. Sci., 49, 743, 10.1167/iovs.07-1072 Shah, 2007, Molecular mechanisms of plaque instability, Curr. Opin. Lipidol., 18, 492, 10.1097/MOL.0b013e3282efa326 Sheraidah, 1993, Correlation between lipids extracted from Bruch's membrane and age, Ophthalmology, 100, 47, 10.1016/S0161-6420(13)31712-6 Shotton, 1995, An introduction to freeze fracture and deep etching, 1 Shoulders, 2005, Current biology of MTP: implications for selective inhibition, Curr. Top. Med. Chem., 5, 283, 10.2174/1568026053544560 de Silva, 1990, A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins, J. Biol. Chem., 265, 13240, 10.1016/S0021-9258(19)38290-0 Sivaprasad, 2005, Bruch's membrane and the vascular intima: is there a common basis for age-related changes and disease?, Clin. Exp. Ophthalmol., 33, 518, 10.1111/j.1442-9071.2005.01074.x Skålen, 2002, Subendothelial retention of atherogenic lipoproteins in early atherosclerosis, Nature, 417, 750, 10.1038/nature00804 Small, 1988, George Lyman Duff memorial lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry, Arteriosclerosis, 8, 103, 10.1161/01.ATV.8.2.103 Small, 1974, Physical-chemical basis of lipid deposition in atherosclerosis, Science, 185, 222, 10.1126/science.185.4147.222 Smith, 1973, Relationship between plasma lipids and arterial tissue lipids, Nutr. Metab., 15, 17, 10.1159/000175418 Smith, 1974, The relationship between plasma and tissue lipids in human atherosclerosis, Adv. Lipid Res., 12, 1, 10.1016/B978-0-12-024912-1.50008-9 Smith, 2002, Apolipoproteins and aging: emerging mechanisms, Ageing Res. Rev., 1, 345, 10.1016/S1568-1637(02)00005-3 Smith, 1967, Lipid in the aortic intima. The correlation of morphological and chemical characteristics, J. Atheroscler. Res., 7, 171, 10.1016/S0368-1319(67)80079-6 Smith, 1972, The microdissection of large atherosclerotic plaques to give morphologically and topographically defined fractions for analysis, Atherosclerosis, 15, 37, 10.1016/0021-9150(72)90036-6 Souied, 1998, The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration, Am. J. Ophthalmol., 125, 353, 10.1016/S0002-9394(99)80146-9 Soutschek, 2004, Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs, Nature, 432, 173, 10.1038/nature03121 Spaide, 1999, Characterization of peroxidized lipids in Bruch's membrane, Retina, 19, 141, 10.1097/00006982-199902000-00010 Sparks, 1981, Hepatic and intestinal contribution of two forms of apolipoprotein B to plasma lipoprotein fractions in the rat, Can. J. Biochem., 59, 693, 10.1139/o81-096 Spraul, 1996, Morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in eyes with age-related macular degeneration, Invest. Ophthalmol. Vis. Sci., 37, 2724 Spraul, 1997, Characteristics of drusen and Bruch's membrane in postmortem eyes with age-related macular degeneration, Arch. Ophthalmol., 115, 267, 10.1001/archopht.1997.01100150269022 Starita, 1996, Hydrodynamics of ageing Bruch's membrane: implications for macular disease, Exp. Eye Res., 62, 565, 10.1006/exer.1996.0066 Starita, 1997, Localization of the site of major resistance to fluid transport in Bruch's membrane, Invest. Ophthalmol. Vis. Sci., 38, 762 Stary, 1992, A definition of the intima of human arteries and of its atherosclerosis-prone regions, Circulation, 85, 391, 10.1161/01.CIR.85.1.391 Steinberg, 2005, Thematic review series: the Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans, J. Lipid Res., 46, 179, 10.1194/jlr.R400012-JLR200 Strunnikova, 2001, Regulated heat shock protein 27 expression in human retinal pigment epithelium, Invest. Ophthalmol. Vis. Sci., 42, 2130 Sun, 2007, Bruch's membrane aging decreases phagocytosis of outer segments by retinal pigment epithelium, Mol. Vis., 13, 2310 Suzuki, 2007, Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration, Mol. Vis., 13, 772 Tabas, 1999, Nonoxidative modifications of lipoproteins in atherogenesis, Annu. Rev. Nutr., 19, 123, 10.1146/annurev.nutr.19.1.123 Tabas, 2007, Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications, Circulation, 116, 1832, 10.1161/CIRCULATIONAHA.106.676890 Tamai, 2002, Lipid hydroperoxide stimulates subretinal choroidal neovascularization in the rabbit, Exp. Eye Res., 74, 301, 10.1006/exer.2001.1121 Tamminen, 1999, Ultrastructure of early lipid accumulation in ApoE-deficient mice, Arterioscler Thromb. Vasc. Biol., 19, 847, 10.1161/01.ATV.19.4.847 Temel, 2007, ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins, J. Lipid Res., 48, 1618, 10.1194/jlr.M700109-JLR200 Tezel, 2004, Reengineering of aged Bruch's membrane to enhance retinal pigment epithelium repopulation, Invest. Ophthalmol. Vis. Sci., 45, 3337, 10.1167/iovs.04-0193 Thakkinstian, 2006, Association between apolipoprotein E polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis, Am. J. Epidemiol., 164, 813, 10.1093/aje/kwj279 Tian, 2005, Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: a comprehensive transcriptional response, Proc. Natl. Acad. Sci. U S A, 102, 11846, 10.1073/pnas.0504759102 Torzewski, 1998, Immunohistochemical demonstration of enzymatically modified human LDL and its colocalization with the terminal complement complex in the early atherosclerotic lesion, Arterioscler Thromb. Vasc. Biol., 18, 369, 10.1161/01.ATV.18.3.369 Triviño, 2006, A cholesterol-enriched diet induces ultrastructural changes in retinal and macroglial rabbit cells, Exp. Eye Res., 83, 357, 10.1016/j.exer.2005.12.020 Tserentsoodol, 2006, Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors, Mol. Vis., 12, 1319 Tserentsoodol, 2006, Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process, Mol. Vis., 12, 1306 Umeda, 2005, Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis), Faseb J., 19, 1683, 10.1096/fj.04-3525fje Vaisar, 2007, Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL, J. Clin. Invest., 117, 746, 10.1172/JCI26206 Varnava, 2002, Relationship between coronary artery remodeling and plaque vulnerability, Circulation, 105, 939, 10.1161/hc0802.104327 Veniant, 2008, Lipoprotein size and susceptibility to atherosclerosis–insights from genetically modified mouse models, Curr. Drug Targets, 9, 174, 10.2174/138945008783755629 Verhoeff, 1926, Basophilic staining of Bruch's membrane, Arch. Ophthalmol., 55, 125 Verschuren, 1995, Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study, JAMA, 274, 131, 10.1001/jama.274.2.131 Walton, 1974, Studies on the pathogenesis of corneal arcus formation. II. Immunofluorescent studies on lipid deposition in the eye of the lipid-fed rabbit, J. Pathol., 114, 217, 10.1002/path.1711140406 Wang, 2001, Oxidative modifications of LDL increase its binding to extracellular matrix from human aortic intima: influence of lesion development, lipoprotein lipase and calcium, J. Pathol., 195, 244, 10.1002/path.935 Wang, 2009, Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration, PLoS ONE, 4, e4160, 10.1371/journal.pone.0004160 Wang, 2009, Lipoprotein particles of intra-ocular origin in human Bruch membrane: an unusual lipid profile, Invest. Ophthalmol. Vis. Sci., 50, 870, 10.1167/iovs.08-2376 Wangsa-Wirawan, 2003, Retinal oxygen: fundamental and clinical aspects, Arch. Ophthalmol., 121, 547, 10.1001/archopht.121.4.547 Waugh, 1984, Identification and detection of in situ cellular and regional differences of lipid composition and class in lipid-rich tissue using hot stage polarizing light microscopy, Lab. Invest., 51, 702 Wetterau, 1992, Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia, Science, 258, 999, 10.1126/science.1439810 Wetterau, 1997, Microsomal triglyceride transfer protein, Biochim. Biophys. Acta, 1345, 136, 10.1016/S0005-2760(96)00168-3 White, 2009, Vasculoprotective effects of apolipoprotein mimetic peptides: an evolving paradigm in HDL therapy, Vasc. Dis. Prev., 6, 122, 10.2174/1567270000906010122 Williams, 1995, The response-to-retention hypothesis of early atherogenesis, Arterioscler Thromb. Vasc. Biol., 15, 551, 10.1161/01.ATV.15.5.551 Williams, 1998, The response-to-retention hypothesis of atherogenesis reinforced, Curr. Opin. Lipidol., 9, 471, 10.1097/00041433-199810000-00012 Williams, 2005, Lipoprotein retention–and clues for atheroma regression, Arterioscler Thromb. Vasc. Biol., 25, 1536, 10.1161/01.ATV.0000174795.62387.d3 Wolter, 1962, Bilateral confluent drusen, Arch. Ophthalmol., 68, 219, 10.1001/archopht.1962.00960030223013 Yamada, 2008, Oxidized low density lipoproteins induce a pathologic response by retinal pigmented epithelial cells, J. Neurochem., 105, 1187, 10.1111/j.1471-4159.2008.05211.x Yao, 1997, Intracellular degradation of newly synthesized apolipoprotein B, J. Lipid Res., 38, 1937, 10.1016/S0022-2275(20)37125-X Yates, 2007, Complement C3 variant and the risk of age-related macular degeneration, N. Engl. J. Med., 357, 553, 10.1056/NEJMoa072618 Yokota, 2001, Delayed-onset ataxia in mice lacking alpha -tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress, PNAS, 98, 15185, 10.1073/pnas.261456098 Young, 1987, Pathophysiology of age-related macular degeneration, Surv. Ophthalmol., 31, 291, 10.1016/0039-6257(87)90115-9 Yuan, 1997, In vitro and in situ magnetic resonance imaging signal features of atherosclerotic plaque-associated lipids, Arterioscler Thromb. Vasc. Biol., 17, 1496, 10.1161/01.ATV.17.8.1496 Zacho, 2008, Genetically elevated C-reactive protein and ischemic vascular disease, N. Engl. J. Med., 359, 1897, 10.1056/NEJMoa0707402 Zak, 2002, Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL, J. Lipid Res., 43, 2164, 10.1194/jlr.M200253-JLR200 Zarbin, 2004, Current concepts in the pathogenesis of age-related macular degeneration, Arch. Ophthalmol., 122, 598, 10.1001/archopht.122.4.598 Zhang, 1996, Apolipoprotein E produced by monocyte-derived macrophages mediates cholesterol efflux that occurs in the absence of added cholesterol acceptors, J. Biol. Chem., 271, 28641, 10.1074/jbc.271.45.28641