Dyslipidemia in age-related macular degeneration.
Journal
Eye (London, England)
ISSN: 1476-5454
Titre abrégé: Eye (Lond)
Pays: England
ID NLM: 8703986
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
04
08
2021
accepted:
15
09
2021
revised:
08
08
2021
pubmed:
13
1
2022
medline:
16
4
2022
entrez:
12
1
2022
Statut:
ppublish
Résumé
Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed at uncovering effective therapeutic strategies have led to the hypothesis that altered lipid metabolism may play a pathogenic role in AMD. This hypothesis is supported by the fact that: (1) drusen, the hallmark histopathologic feature of AMD, are composed of lipids, (2) polymorphisms of genes involved in lipid homeostasis are associated with increased odds of AMD, (3) metabolomics studies show that patients with AMD have alterations in metabolites from lipid pathways, and (4) alterations in serum lipid profiles as a reflection of systemic dyslipidemia are associated with AMD. There is strong evidence that statins, which are well described for treating dyslipidemia and reducing risk associated with cardiovascular disease, may have a role for treating certain cohorts of AMD patients, but this has yet to be conclusively proven. Of interest, the specific changes in serum lipoprotein profiles associated with decreased cardiovascular risk (i.e., high HDL levels) have been shown in some studies to be associated with increased risk of AMD. In this review, we highlight the evidence that supports a role for altered lipid metabolism in AMD and provide our perspective regarding the remaining questions that need to be addressed before lipid-based therapies can emerge for specific cohorts of AMD patients. 摘要: 富含脂质的玻璃疣是年龄相关性黄斑变性 (AMD) 的重要特征, AMD是发达国家老年人失明的主要原因。为发现有效的治疗策略提出了一个假说, 即脂质代谢的改变可能在AMD中起致病作用。这一假说目前有以下事实支持: (1) 作为AMD标志性组织病理学特征的玻璃疣是由脂质组成, (2) 参与脂质稳态的基因多态性与AMD的患病几率增加有关, (3) 代谢组学研究表明AMD患者的脂质代谢产物发生了改变, 以及4) 反映全身性血脂异常的血脂谱变化与AMD有关。有强有力的证据表明, 他汀类药物可能在治疗某些AMD患者的队列中发挥作用, 但这一观点尚未得到确凿的证明, 且他汀类药物在治疗血脂异常和降低与心血管疾病相关的风险方面得到了证实。有趣的是, 一些研究表明, 血清脂蛋白谱中与心血管风险降低 (即高密度脂蛋白水平) 相关的特定变化与AMD风险增加有关。在这篇综述中, 我们强调了支持脂质代谢改变在AMD中作用的证据, 并就AMD患者特定队列中在脂质治疗前需要解决的问题提出了我们的观点。.
Autres résumés
Type: Publisher
(chi)
摘要: 富含脂质的玻璃疣是年龄相关性黄斑变性 (AMD) 的重要特征, AMD是发达国家老年人失明的主要原因。为发现有效的治疗策略提出了一个假说, 即脂质代谢的改变可能在AMD中起致病作用。这一假说目前有以下事实支持: (1) 作为AMD标志性组织病理学特征的玻璃疣是由脂质组成, (2) 参与脂质稳态的基因多态性与AMD的患病几率增加有关, (3) 代谢组学研究表明AMD患者的脂质代谢产物发生了改变, 以及4) 反映全身性血脂异常的血脂谱变化与AMD有关。有强有力的证据表明, 他汀类药物可能在治疗某些AMD患者的队列中发挥作用, 但这一观点尚未得到确凿的证明, 且他汀类药物在治疗血脂异常和降低与心血管疾病相关的风险方面得到了证实。有趣的是, 一些研究表明, 血清脂蛋白谱中与心血管风险降低 (即高密度脂蛋白水平) 相关的特定变化与AMD风险增加有关。在这篇综述中, 我们强调了支持脂质代谢改变在AMD中作用的证据, 并就AMD患者特定队列中在脂质治疗前需要解决的问题提出了我们的观点。.
Identifiants
pubmed: 35017697
doi: 10.1038/s41433-021-01780-y
pii: 10.1038/s41433-021-01780-y
pmc: PMC8807842
doi:
Substances chimiques
Lipids
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
312-318Subventions
Organisme : NEI NIH HHS
ID : P30 EY026877
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030088
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.
Références
Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:e106–16.
pubmed: 25104651
doi: 10.1016/S2214-109X(13)70145-1
Vavvas DG, Small KW, Awh CC, Zanke BW, Tibshirani RJ, Kustra R. CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation. Proc Natl Acad Sci USA. 2018;115:E696–704.
pubmed: 29311295
pmcid: 5789949
doi: 10.1073/pnas.1718059115
Chew EY, Clemons TE, Agrón E, Sperduto RD, Sangiovanni JP, Kurinij N, et al. Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology. 2013;120:1604–11.e4.
pubmed: 23582353
doi: 10.1016/j.ophtha.2013.01.021
Wang L, Clark ME, Crossman DK, Kojima K, Messinger JD, Mobley JA, et al. Abundant lipid and protein components of drusen. PLoS ONE. 2010;5:e10329.
pubmed: 20428236
pmcid: 2859054
doi: 10.1371/journal.pone.0010329
Curcio CA, Johnson M, Rudolf M, Huang J-D. The oil spill in ageing Bruch membrane. Br J Ophthalmol. 2011;95:1638–45.
pubmed: 21890786
doi: 10.1136/bjophthalmol-2011-300344
Curcio CA. Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies. Investig Ophthalmol Vis Sci. 2018;59:AMD160–81.
doi: 10.1167/iovs.18-24882
Schmidt S, Klaver C, Saunders A, Postel E, De La Paz M, Agarwal A, et al. A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy. Ophthalmic Genet. 2002;23:209–23.
pubmed: 12567264
doi: 10.1076/opge.23.4.209.13883
Klaver CC, Kliffen M, van Duijn CM, Hofman A, Cruts M, Grobbee DE, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet. 1998;63:200–6.
pubmed: 9634502
pmcid: 1377225
doi: 10.1086/301901
Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, 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 USA. 2010;107:7395–400.
pubmed: 20385826
pmcid: 2867697
doi: 10.1073/pnas.0912019107
Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci USA. 2010;107:7401–6.
pubmed: 20385819
pmcid: 2867722
doi: 10.1073/pnas.0912702107
Fritsche LG, Igl W, Bailey JNC, Grassmann F, Sengupta S, Bragg-Gresham JL, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48:134–43.
pubmed: 26691988
doi: 10.1038/ng.3448
Wang Y, Wang M, Zhang X, Zhang Q, Nie J, Zhang M, et al. The association between the lipids levels in blood and risk of age-related macular degeneration. Nutrients. 2016;8:663.
Colijn JM, den Hollander AI, Demirkan A, Cougnard-Grégoire A, Verzijden T, Kersten E, et al. Increased high-density lipoprotein levels associated with age-related macular degeneration: evidence from the EYE-RISK and European Eye Epidemiology Consortia. Ophthalmology. 2019;126:393–406.
pubmed: 30315903
doi: 10.1016/j.ophtha.2018.09.045
Yip JLY, Khawaja AP, Chan MPY, Broadway DC, Peto T, Tufail A, et al. Cross sectional and longitudinal associations between cardiovascular risk factors and age related macular degeneration in the EPIC-Norfolk Eye Study. PLoS ONE. 2015;10:e0132565.
pubmed: 26176222
pmcid: 4503731
doi: 10.1371/journal.pone.0132565
Burgess S, Davey, Smith G. Mendelian randomization implicates high-density lipoprotein cholesterol-associated mechanisms in etiology of age-related macular degeneration. Ophthalmology. 2017;124:1165–74.
pubmed: 28456421
doi: 10.1016/j.ophtha.2017.03.042
Curcio CA, Millican CL. Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol. 1999;117:329–39.
pubmed: 10088810
doi: 10.1001/archopht.117.3.329
Sarks S, Cherepanoff S, Killingsworth M, Sarks J. Relationship of Basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration. Investig Ophthalmol Vis Sci. 2007;48:968–77.
doi: 10.1167/iovs.06-0443
Bressler NM, Silva JC, Bressler SB, Fine SL, Green WR. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina. 1994;14:130–42.
pubmed: 8036323
doi: 10.1097/00006982-199414020-00006
Curcio CA. Antecedents of soft drusen, the specific deposits of age-related macular degeneration, in the biology of human macula. Investig Ophthalmol Vis Sci. 2018;59:AMD182–94.
doi: 10.1167/iovs.18-24883
Chen L, Messinger JD, Kar D, Duncan JL, Curcio CA. Biometrics, impact, and significance of basal linear deposit and subretinal drusenoid deposit in age-related macular degeneration. Investig Ophthalmol Vis Sci. 2021;62:33.
doi: 10.1167/iovs.62.1.33
Ferris FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844–51.
pubmed: 23332590
doi: 10.1016/j.ophtha.2012.10.036
Ferris FL, Davis MD, Clemons TE, Lee L-Y, Chew EY, Lindblad AS, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570–4.
pubmed: 16286620
doi: 10.1001/archopht.123.11.1570
Nathoo NA, Or C, Young M, Chui L, Fallah N, Kirker AW, et al. Optical coherence tomography-based measurement of drusen load predicts development of advanced age-related macular degeneration. Am J Ophthalmol. 2014;158:757–61.e1.
pubmed: 24983793
doi: 10.1016/j.ajo.2014.06.021
Folgar FA, Yuan EL, Sevilla MB, Chiu SJ, Farsiu S, Chew EY, et al. Drusen volume and retinal pigment epithelium abnormal thinning volume predict 2-year progression of age-related macular degeneration. Ophthalmology. 2016;123:39–50.e1.
pubmed: 26578448
doi: 10.1016/j.ophtha.2015.09.016
Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, et al. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA. 2002;99:14682–7.
pubmed: 12391305
pmcid: 137479
doi: 10.1073/pnas.222551899
Bergen AA, Arya S, Koster C, Pilgrim MG, Wiatrek-Moumoulidis D, van der Spek PJ, et al. On the origin of proteins in human drusen: the meet, greet and stick hypothesis. Prog Retin Eye Res. 2019;70:55–84.
pubmed: 30572124
doi: 10.1016/j.preteyeres.2018.12.003
Fernández-Vega B, García M, Olivares L, Álvarez L, González-Fernández A, Artime E, et al. The association study of lipid metabolism gene polymorphisms with AMD identifies a protective role for APOE-E2 allele in the wet form in a Northern Spanish population. Acta Ophthalmol. 2020;98:e282–91.
pubmed: 31654486
doi: 10.1111/aos.14280
Han X, Gharahkhani P, Mitchell P, Liew G, Hewitt AW, MacGregor S. Genome-wide meta-analysis identifies novel loci associated with age-related macular degeneration. J Hum Genet. 2020;65:657–65.
pubmed: 32277175
doi: 10.1038/s10038-020-0750-x
Laíns I, Kelly RS, Miller JB, Silva R, Vavvas DG, Kim IK, et al. Human plasma metabolomics study across all stages of age-related macular degeneration identifies potential lipid biomarkers. Ophthalmology. 2018;125:245–54.
pubmed: 28916333
doi: 10.1016/j.ophtha.2017.08.008
Acar İE, Lores-Motta L, Colijn JM, Meester-Smoor MA, Verzijden T, Cougnard-Gregoire A, et al. Integrating metabolomics, genomics, and disease pathways in age-related macular degeneration: the EYE-RISK consortium. Ophthalmology. 2020;127:1693–709.
pubmed: 32553749
doi: 10.1016/j.ophtha.2020.06.020
Albrink MJ, Fasanella RM. Serum lipids in patients with senile macular degeneration. Am J Ophthalmol. 1963;55:709–13.
pubmed: 14011774
doi: 10.1016/0002-9394(63)92428-0
Vidaurri JS, Pe’er J, Halfon ST, Halperin G, Zauberman H. Association between drusen and some of the risk factors for coronary artery disease. Ophthalmologica. 1984;188:243–7.
pubmed: 6204260
doi: 10.1159/000309370
Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MO. Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol. 1988;128:700–10.
pubmed: 3421236
doi: 10.1093/oxfordjournals.aje.a115023
Ferris FL. Senile macular degeneration: review of epidemiologic features. Am J Epidemiol. 1983;118:132–51.
pubmed: 6192710
doi: 10.1093/oxfordjournals.aje.a113624
Anon. Risk factors for neovascular age-related macular degeneration. The eye disease case-control study group. Arch Ophthalmol. 1992;110:1701–8.
Klein R, Klein BE, Franke T. The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1993;100:406–14.
pubmed: 8460013
doi: 10.1016/S0161-6420(93)31634-9
Klein R, Klein BEK, 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;110:1273–80.
pubmed: 12799274
doi: 10.1016/S0161-6420(03)00599-2
Hyman L, Schachat AP, He Q, Leske MC. Hypertension, cardiovascular disease, and age-related macular degeneration. Age-related macular degeneration risk factors study group. Arch Ophthalmol. 2000;118:351–8.
pubmed: 10721957
doi: 10.1001/archopht.118.3.351
van Leeuwen R, Klaver CCW, Vingerling JR, Hofman A, van Duijn CM, Stricker BHC, et al. Cholesterol and age-related macular degeneration: is there a link? Am J Ophthalmol. 2004;137:750–2.
pubmed: 15059717
doi: 10.1016/j.ajo.2003.09.015
Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology. 2004;111:1280–7.
pubmed: 15234127
doi: 10.1016/j.ophtha.2003.11.010
Dashti N, McGwin G, Owsley C, Curcio CA. Plasma apolipoproteins and risk for age related maculopathy. Br J Ophthalmol. 2006;90:1028–33.
pubmed: 16723359
pmcid: 1857205
doi: 10.1136/bjo.2006.093856
Klein R, Myers CE, Buitendijk GHS, Rochtchina E, Gao X, de Jong PTVM, et al. Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium. Am J Ophthalmol. 2014;158:513–24.e3.
pubmed: 24879949
pmcid: 4138281
doi: 10.1016/j.ajo.2014.05.027
Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, Zlateva G, et al. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. 2010;10:31.
pubmed: 21144031
pmcid: 3009619
doi: 10.1186/1471-2415-10-31
Sasaki M, Harada S, Kawasaki Y, Watanabe M, Ito H, Tanaka H, et al. Gender-specific association of early age-related macular degeneration with systemic and genetic factors in a Japanese population. Sci Rep. 2018;8:785.
pubmed: 29335418
pmcid: 5768785
doi: 10.1038/s41598-017-18487-4
Fan Q, Maranville JC, Fritsche L, Sim X, Cheung CMG, Chen LJ, et al. HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization. Int J Epidemiol. 2017;46:1891–902.
pubmed: 29025108
pmcid: 5837540
doi: 10.1093/ije/dyx189
Han X, Ong J-S, Hewitt AW, Gharahkhani P, MacGregor S. The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study. Int J Epidemiol. 2021;50:325–36.
pubmed: 33211829
doi: 10.1093/ije/dyaa178
Lüdtke L, Jürgens C, Ittermann T, Völzke H, Tost F. Age-related macular degeneration and associated risk factors in the population-based study of health in pomerania (SHIP-Trend). Med Sci Monit. 2019;25:6383–90.
pubmed: 31446436
pmcid: 6724561
doi: 10.12659/MSM.915493
Mao F, Yang X, Yang K, Cao X, Cao K, Hao J, et al. Six-year incidence and risk factors for age-related macular degeneration in a rural Chinese population: the Handan Eye study. Investig Ophthalmol Vis Sci. 2019;60:4966–71.
doi: 10.1167/iovs.19-27325
Kelly UL, Grigsby D, Cady MA, Landowski M, Skiba NP, Liu J, et al. High-density lipoproteins are a potential therapeutic target for age-related macular degeneration. J Biol Chem. 2020;295:13601–16.
pubmed: 32737203
pmcid: 7521644
doi: 10.1074/jbc.RA119.012305
Gehlbach P, Li T, Hatef E. Statins for age-related macular degeneration. Cochrane Database Syst Rev. 2016;2016:CD006927.
van Leeuwen R, Vingerling JR, Hofman A, de Jong PTVM, Stricker BHC. Cholesterol lowering drugs and risk of age related maculopathy: prospective cohort study with cumulative exposure measurement. BMJ. 2003;326:255–6.
pubmed: 12560276
pmcid: 140763
doi: 10.1136/bmj.326.7383.255
Wilson HL, Schwartz DM, Bhatt HRF, McCulloch CE, Duncan JL. Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration. Am J Ophthalmol. 2004;137:615–24.
pubmed: 15059698
VanderBeek BL, Zacks DN, Talwar N, Nan B, Stein JD. Role of statins in the development and progression of age-related macular degeneration. Retina. 2013;33:414–22.
pubmed: 23314233
pmcid: 3939714
doi: 10.1097/IAE.0b013e318276e0cf
Mast N, Bederman IR, Pikuleva IA. Retinal Cholesterol Content Is Reduced In Simvastatin-treated Mice Due To Inhibited Local Biosynthesis Albeit Increased Uptake Of Serum Cholesterol. Drug Metab Dispos. 2018;46:1528–37.
pubmed: 30115644
pmcid: 6193214
doi: 10.1124/dmd.118.083345
Vavvas DG, Daniels AB, Kapsala ZG, Goldfarb JW, Ganotakis E, Loewenstein JI, et al. Regression of some high-risk features of age-related macular degeneration (AMD) in patients receiving intensive statin treatment. EBioMedicine. 2016;5:198–203.
pubmed: 27077128
pmcid: 4816836
doi: 10.1016/j.ebiom.2016.01.033
Guymer RH, Baird PN, Varsamidis M, Busija L, Dimitrov PN, Aung KZ, et al. Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. PLoS ONE. 2013;8:e83759.
pubmed: 24391822
pmcid: 3877099
doi: 10.1371/journal.pone.0083759
Wang K, Hsieh M-J, Chien H-W, Lee C-Y, Yeh C-B, Huang J-Y, et al. Medical compliance of fibrate and the decreased risk of age-related macular degeneration in dyslipidemia-related diseases: a population-based cohort study. Int J Environ Res Public Health. 2021;18:E301.
pubmed: 33401577
doi: 10.3390/ijerph18010301
Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.
pubmed: 14996776
doi: 10.1001/jama.291.9.1071
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.
pubmed: 15007110
doi: 10.1056/NEJMoa040583
Sacks FM, Liang L, Furtado JD, Cai T, Davidson WS, He Z, et al. Protein-defined subspecies of HDLs (High-density lipoproteins) and differential risk of coronary heart disease in 4 prospective studies. Arterioscler Thromb Vasc Biol. 2020;40:2714–27.
pubmed: 32907368
pmcid: 7577984
doi: 10.1161/ATVBAHA.120.314609
Lin JB, Mast N, Bederman IR, Li Y, Brunengraber H, Björkhem I, et al. Cholesterol in mouse retina originates primarily from in situ de novo biosynthesis. J Lipid Res. 2016;57:258–64.
pubmed: 26630912
pmcid: 4727421
doi: 10.1194/jlr.M064469
Sene A, Khan AA, Cox D, Nakamura REI, Santeford A, Kim BM, et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013;17:549–61.
pubmed: 23562078
pmcid: 3640261
doi: 10.1016/j.cmet.2013.03.009
van der Kant R, Langness VF, Herrera CM, Williams DA, Fong LK, Leestemaker Y, et al. Cholesterol metabolism is a druggable axis that independently regulates tau and amyloid-β in iPSC-derived Alzheimer’s disease neurons. Cell Stem Cell. 2019;24:363–75.e9.
pubmed: 30686764
pmcid: 6414424
doi: 10.1016/j.stem.2018.12.013
Kosowski M, Smolarczyk-Kosowska J, Hachuła M, Maligłówka M, Basiak M, Machnik G, et al. The effects of statins on neurotransmission and their neuroprotective role in neurological and psychiatric disorders. Molecules. 2021;26:2838.
pubmed: 34064670
pmcid: 8150718
doi: 10.3390/molecules26102838