Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis

Journal of Clinical Investigation

Volumn 122, Issue 8, 2012, Pages 3012-3023

  Omarova, Saida ^a   Charvet, Casey D ^a   Reem, Rachel E ^a,e   Mast, Natalia ^a   Zheng, Wenchao ^a   Huang, Suber ^a,b   Peachey, Neal S ^a,c,d   Pikuleva, Irina A ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^c LERNER RESEARCH INSTITUTE   (United States)

^d LOUIS STOKES CLEVELAND VA MEDICAL CENTER   (United States)

^e THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTANETRIOL 26 MONOOXYGENASE; CHOLESTEROL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOSYNTHESIS; CELL ACTIVATION; CHOLESTEROL METABOLISM; CHOROID; CONTROLLED STUDY; CYP27A1 GENE; EXPERIMENTAL MODEL; FEMALE; GENE; HYPOXEMIA; IMMUNOHISTOCHEMISTRY; LIPID STORAGE; MALE; MOUSE; MUELLER CELL; NONHUMAN; PIGMENT EPITHELIUM; PRIORITY JOURNAL; RETINA BLOOD FLOW; RETINA BLOOD VESSEL; RETINA MACULA AGE RELATED DEGENERATION; SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY; SUBRETINAL NEOVASCULARIZATION; UPREGULATION;

ANIMALS; CHOLESTEROL; CHOROID; CYTOCHROME P-450 CYP27A1; DISEASE MODELS, ANIMAL; FEMALE; HOMEOSTASIS; HUMANS; MACULAR DEGENERATION; MALE; MICE; MICE, KNOCKOUT; NEOVASCULARIZATION, PATHOLOGIC; RETINA; RETINAL VESSELS;

EID: 84864741066     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI63816     Document Type: Article

References (95)

1. Pascolini D, et al. 2002 global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic Epidemiol. 2004;11(2):67-115. (Pubitemid 38530465)
2. Gass JD. Atlas of Macular Diseases. St. Louis, Missouri, USA: CV Mosby; 1997.
3. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina. 2008;28(3):375-384. (Pubitemid 351354939)
4. Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85(3):845-881. (Pubitemid 40885218)
5. Ghazi NG. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2002;22(4):509-511.
6. de Jong PT. Age-related macular degeneration. N Engl J Med. 2006;355(14):1474-1485.
7. Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 2009;28(1):1-18.
8. Abdelsalam A, Del Priore L, Zarbin MA. Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Surv Ophthalmol. 1999;44(1):1-29. (Pubitemid 29378350)
9. Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP. Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br J Ophthalmol. 1999;83(3):358-368. (Pubitemid 29112419)
10. Curcio CA, Johnson M, Rudolf M, Huang JD. The oil spill in ageing Bruch membrane. Br J Ophthalmol. 2011;95(12):1638-1645.
11. Malek G, Li CM, Guidry C, Medeiros NE, Curcio CA. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am J Pathol. 2003;162(2):413-425. (Pubitemid 36267849)
12. Wang L, et al. Abundant lipid and protein components of drusen. PLoS One. 2010;5(4):e10329.
13. Klaver CC, et al. Incidence and progression rates of age-related maculopathy: the Rotterdam Study. Invest Ophthalmol Vis Sci. 2001;42(10):2237-2241. (Pubitemid 32848852)
14. Mitchell P, Wang JJ, Foran S, Smith W. Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study. Ophthalmology. 2002;109(6):1092-1097. (Pubitemid 34546916)
15. Klein R, Klein BE, Tomany SC, Cruickshanks KJ. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. Ophthalmology. 2003;110(4):636-643. (Pubitemid 36520056)
16. Tomany SC, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology. 2004;111(7):1280-1287. (Pubitemid 38844822)
17. van Leeuwen R, et al. Cholesterol and age-related macular degeneration: is there a link? Am J Ophthalmol. 2004;137(4):750-752.
18. Souied EH, et al. The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration. Am J Ophthalmol. 1998;125(3):353-359. (Pubitemid 28124364)
19. Klaver CC, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet. 1998;63(1):200-206. (Pubitemid 30428336)
20. Neale BM, et al. Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci U S A. 2010;107(16):7395-7400.
21. Chen W, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A. 2010;107(16):7401-7406.
22. Yu Y, Reynolds R, Rosner B, Daly MJ, Seddon JM. Prospective assessment of genetic effects on progression to different stages of age-related macular degeneration using multi-state markov models. Invest Ophthalmol Vis Sci. 2012;53(3):1548-1556.
23. Fliesler SJ, Bretillon L. The ins and outs of cholesterol in the vertebrate retina. J Lipid Res. 2010;51(12):3399-3413.
24. Edwards AO, Malek G. Molecular genetics of AMD and current animal models. Angiogenesis. 2007;10(2):119-132. (Pubitemid 46440627)
25. Zeiss CJ. Animals as models of age-related macular degeneration: an imperfect measure of the truth. Vet Pathol. 2010;47(3):396-413.
26. Pikuleva IA. Cytochrome P450s and cholesterol homeostasis. Pharmacol Ther. 2006;112(3):761-773. (Pubitemid 44573496)
27. Liao WL, et al. Quantification of cholesterol-metabolizing P450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzyme-product correlations in human retina but not human brain. J Proteome Res. 2011;10(1):241-248.
28. Mast N, et al. Cholestenoic acid is an important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism to that in the brain. Invest Ophthalmol Vis Sci. 2011;52(1):594-603.
29. Bjorkhem I, Boberg KM, Leitersdorf E. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Scriver AL, Beaudet AL, Sly WS, Valle D, Childs B, eds. The Metabolic And Molecular Bases Of Inherited Disease. New York, New York, USA: McGraw-Hill; 1995:2073-2099.
30. Bjorkhem I, Hansson M. Cerebrotendinous xanthomatosis: an inborn error in bile acid synthesis with defined mutations but still a challenge. Biochem Biophys Res Commun. 2010;396(1):46-49.
31. Cruysberg JR, Wevers RA, van Engelen BG, Pinckers A, van Spreeken A, Tolboom JJ. Ocular and systemic manifestations of cerebrotendinous xanthomatosis. Am J Ophthalmol. 1995;120(5):597-604.
32. Morgan SJ, McKenna P, Bosanquet RC. Case of cerebrotendinous xanthomatosis. I: Unusual ophthalmic features. Br J Ophthalmol. 1989;73(12):1011-1014. (Pubitemid 20029893)
33. Dotti MT, Rufa A, Federico A. Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings. J Inherit Metab Dis. 2001;24(7):696-706. (Pubitemid 34023878)
34. Rosen H, et al. Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. J Biol Chem. 1998;273(24):14805-14812. (Pubitemid 28272767)
35. Repa JJ, et al. Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding. J Biol Chem. 2000;275(50):39685-39692. (Pubitemid 32058997)
36. Honda A, et al. Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27(-/-) mice and CTX. J Lipid Res. 2001;42(2):291-300. (Pubitemid 32206842)
37. Dubrac S, et al. Role of CYP27A in cholesterol and bile acid metabolism. J Lipid Res. 2005;46(1):76-85. (Pubitemid 40066673)
38. Bavner A, et al. On the mechanism of accumulation of cholestanol in the brain of mice with a disruption of sterol 27-hydroxylase. J Lipid Res. 2010;51(9):2722-2730.
39. Coscas F, Coscas G, Souied E, Tick S, Soubrane G. Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2007;144(4):592-599.
40. Campos M, Amaral J, Becerra SP, Fariss RN. A novel imaging technique for experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2006;47(12):5163-5170. (Pubitemid 46723759)
41. Lin M, et al. Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Muller cells. Diabetologia. 2011;54(6):1554-1566.
42. Loewen N, Chen J, Dudley VJ, Sarthy VP, Mathura JR Jr. Genomic response of hypoxic Muller cells involves the very low density lipoprotein receptor as part of an angiogenic network. Exp Eye Res. 2009;88(5):928-937.
43. Shen X, Zhong Y, Xie B, Cheng Y, Jiao Q. Pigment epithelium derived factor as an anti-inflammatory factor against decrease of glutamine synthetase expression in retinal Muller cells under high glucose conditions. Graefes Arch Clin Exp Ophthalmol. 2010;248(8):1127-1136.
44. Kuzmanovic M, Dudley VJ, Sarthy VP. GFAP promoter drives Muller cell-specific expression in transgenic mice. Invest Ophthalmol Vis Sci. 2003;44(8):3606-3613. (Pubitemid 36909802)
45. Wu KH, Madigan MC, Billson FA, Penfold PL. Differential expression of GFAP in early v late AMD: a quantitative analysis. Br J Ophthalmol. 2003;87(9):1159-1166. (Pubitemid 37064896)
46. Querques G, Avellis FO, Querques L, Massamba N, Bandello F, Souied EH. Three dimensional spectral domain optical coherence tomography features of retinal-choroidal anastomosis. Graefes Arch Clin Exp Ophthalmol. 2011;250(2):165-173.
47. Stefansson E, Geirsdottir A, Sigurdsson H. Metabolic physiology in age related macular degeneration. Prog Retin Eye Res. 2010;30(1):72-80.
48. Varia MA, et al. Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecol Oncol. 1998;71(2):270-277. (Pubitemid 28550812)
49. Jiang BH, Semenza GL, Bauer C, Marti HH. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am JPhysiol. 1996;271(4 pt 1):C1172-1180.
50. Kizaka-Kondoh S, Tanaka S, Harada H, Hiraoka M. The HIF-1-active microenvironment: an environmental target for cancer therapy. Adv Drug Deliv Rev. 2009;61(7-8):623-632.
51. Jankovic B, et al. Comparison between pimonidazole binding, oxygen electrode measurements, and expression of endogenous hypoxia markers in cancer of the uterine cervix. Cytometry B Clin Cytom. 2006;70(2):45-55.
52. Sobhanifar S, Aquino-Parsons C, Stanbridge EJ, Olive P. Reduced expression of hypoxia-inducible factor-1alpha in perinecrotic regions of solid tumors. Cancer Res. 2005;65(16):7259-7266. (Pubitemid 41161257)
53. Castanho MA, Coutinho A, Prieto MJ. Absorption and fluorescence spectra of polyene antibiotics in the presence of cholesterol. J Biol Chem. 1992;267(1):204-209.
54. Curcio CA, Presley JB, Malek G, Medeiros NE, Avery DV, Kruth HS. Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp Eye Res. 2005;81(6):731-741. (Pubitemid 41790421)
55. Curcio CA, Millican CL, Bailey T, Kruth HS. Accumulation of cholesterol with age in human Bruch's membrane. Invest Ophthalmol Vis Sci. 2001;42(1):265-274. (Pubitemid 32059440)
56. Turley SD, Schwarz M, Spady DK, Dietschy JM. Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets. Hepatology. 1998;28(4):1088-1094. (Pubitemid 28450271)
57. Bojanic DD, et al. Differential expression and function of ABCG1 and ABCG4 during development and aging. J Lipid Res. 2010;51(1):169-181.
58. Tserentsoodol N, et al. Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process. Mol Vis. 2006;12:1306-1318. (Pubitemid 44688464)
59. Fliesler SJ, Florman R, Rapp LM, Pittler SJ, Keller RK. In vivo biosynthesis of cholesterol in the rat retina. FEBS Lett. 1993;335(2):234-238. (Pubitemid 23350413)
60. Fliesler SJ, Keller RK. Isoprenoid metabolism in the vertebrate retina. Int J Biochem Cell Biol. 1997;29(6):877-894. (Pubitemid 27364160)
61. Elner VM. Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids. Trans Am Ophthalmol Soc. 2002;100:301-338. (Pubitemid 37039377)
62. Curcio CA, Johnson M, Huang JD, Rudolf M. Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration. J Lipid Res. 2010;51(3):451-467.
63. Tserentsoodol N, Gordiyenko NV, Pascual I, Lee JW, Fliesler SJ, Rodriguez IR. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors. Mol Vis. 2006;12:1319-1333. (Pubitemid 44688463)
64. Bretillon L, et al. Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina. Curr Eye Res. 2007;32(4):361-366. (Pubitemid 46633860)
65. Ramirez DM, Andersson S, Russell DW. Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. J Comp Neurol. 2008;507(5):1676-1693. (Pubitemid 351468217)
66. Lund E, Sisfontes L, Reihner E, Bjorkhem I. Determination of serum levels of unesterified lathosterol by isotope dilution-mass spectrometry. Scand J Clin Lab Invest. 1989;49(2):165-171. (Pubitemid 19112173)
67. Kotti TJ, Ramirez DM, Pfeiffer BE, Huber KM, Russell DW. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci U S A. 2006;103(10):3869-3874. (Pubitemid 43376647)
68. Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T. Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem. 2009;78:1017-1040.
69. Pikuleva I, Javitt NB. Novel sterols synthesized via the CYP27A1 metabolic pathway. Arch Biochem Biophys. 2003;420(1):35-39. (Pubitemid 37393371)
70. Guarneri P, Guarneri R, Cascio C, Pavasant P, Piccoli F, Papadopoulos V. Neurosteroidogenesis in rat retinas. J Neurochem. 1994;63(1):86-96. (Pubitemid 24184905)
71. Jaliffa CO, et al. Effect of neurosteroids on the retinal gabaergic system and electroretinographic activity in the golden hamster. J Neurochem. 2005;94(6):1666-1675. (Pubitemid 41324647)
72. Lee JW, Fuda H, Javitt NB, Strott CA, Rodriguez IR. Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina. Exp Eye Res. 2006;83(2):465-469. (Pubitemid 43850940)
73. Heo GY, Liao WL, Turko IV, Pikuleva IA. Features of the retinal environment which affect the activities and product profile of cholesterol-metabolizing cytochromes P450 CYP27A1 and CYP11A1. Arch Biochem Biophys. 2012;518(2):119-126.
74. Heo GY, Bederman I, Mast N, Liao WL, Turko IV, Pikuleva IA. Conversion of 7-ketocholesterol to oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells. J Lipid Res. 2011;52(6):1117-1127.
75. Rodriguez IR, Larrayoz IM. Cholesterol oxidation in the retina: Implications of 7-ketocholesterol formation in chronic inflammation and age-related macular degeneration. J Lipid Res. 2010;51(10):2847-2862.
76. Curcio CA, Johnson M, Huang JD, Rudolf M. Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins. Prog Retin Eye Res. 2009;28(6):393-422.
77. DeBose-Boyd RA. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 2008;18(6):609-621. (Pubitemid 351793117)
78. Pfrieger FW. Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci. 2003;60(6):1158-1171. (Pubitemid 36791918)
79. Shaw G, Weber K. The intermediate filament complement of the retina: a comparison between different mammalian species. Eur J Cell Biol. 1984;33(1):95-104. (Pubitemid 14158642)
80. Dreher Z, Robinson SR, Distler C. Muller cells in vascular and avascular retinae: a survey of seven mammals. J Comp Neurol. 1992;323(1):59-80.
81. Madigan MC, Penfold PL, Provis JM, Balind TK, Billson FA. Intermediate filament expression in human retinal macroglia. Histopathologic changes associated with age-related macular degeneration. Retina. 1994;14(1):65-74. (Pubitemid 24119506)
82. Heckenlively JR, et al. Mouse model of subretinal neovascularization with choroidal anastomosis. Retina. 2003;23(4):518-522. (Pubitemid 37071966)
83. Okamoto N, et al. Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization. Am J Pathol. 1997;151(1):281-291.
84. Chen Y, Hu Y, Moiseyev G, Zhou KK, Chen D, Ma JX. Photoreceptor degeneration and retinal inflammation induced by very low-density lipoprotein receptor deficiency. Microvasc Res. 2009;78(1):119-127.
85. Chen Y, Hu Y, Lu K, Flannery JG, Ma JX. Very low density lipoprotein receptor, a negative regulator of the wnt signaling pathway and choroidal neovascularization. J Biol Chem. 2007;282(47):34420-34428. (Pubitemid 350159486)
86. Zhou X, Wong LL, Karakoti AS, Seal S, McGinnis JF. Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the Vldlr knockout mouse. PLoS One. 2011;6(2):e16733.
87. Li C, et al. Biochemical alterations in the retinas of very low-density lipoprotein receptor knockout mice: an animal model of retinal angiomatous proliferation. Arch Ophthalmol. 2007;125(6):795-803. (Pubitemid 46919741)
88. Hua J, et al. Resveratrol inhibits pathologic retinal neovascularization in Vldlr(-/-) mice. Invest Ophthalmol Vis Sci. 2011;52(5):2809-2816.
89. Sirvent A, et al. The farnesoid X receptor induces very low density lipoprotein receptor gene expression. FEBS Lett. 2004;566(1-3):173-177. (Pubitemid 38625954)
90. Hu W, et al. Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model's retinal angiomatous proliferation. Invest Ophthalmol Vis Sci. 2008;49(1):407-415.
91. Hong C, et al. The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2. J Biol Chem. 2010;285(26):19720-19726.
92. Janowski BA, et al. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci U S A. 1999;96(1):266-271. (Pubitemid 29036088)
93. Song C, Liao S. Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Endocrinology. 2000;141(11):4180-4184.
94. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996;383(6602):728-731. (Pubitemid 26360651)
95. Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model. Retina. 2011;31(8):1609-1619.