Age-related macular degeneration: A disease of extracellular complement amplification

被引:26
作者
de Jong, Sarah [1 ,2 ]
Tang, Jiaqi [1 ,2 ]
Clark, Simon J. [1 ,2 ,3 ]
机构
[1] Eberhard Karls Univ Tubingen, Univ Eye Clin, Dept Ophthalmol, Tubingen, Germany
[2] Eberhard Karls Univ Tubingen, Inst Ophthalm Res, Dept Ophthalmol, Tubingen, Germany
[3] Univ Manchester, Fac Biol Med & Hlth, Lydia Becker Inst Immunol & Inflammat, Manchester, Lancs, England
关键词
age-related macular degeneration; complement system; extracellular matrix remodeling; MEMBRANE ATTACK COMPLEX; RARE GENETIC-VARIANTS; LOW-FREQUENCY VARIANTS; FACTOR-H POLYMORPHISM; C-REACTIVE PROTEIN; ALTERNATIVE PATHWAY; BRUCHS MEMBRANE; HIGH-RISK; CFI GENE; REGULATORY PROTEINS;
D O I
10.1111/imr.13145
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Age-related macular degeneration (AMD) is a major cause of vision impairment in the Western World, and with the aging world population, its incidence is increasing. As of today, for the majority of patients, no treatment exists. Multiple genetic and biochemical studies have shown a strong association with components in the complement system and AMD, and evidence suggests a major role of remodeling of the extracellular matrix underlying the outer blood/retinal barrier. As part of the innate immune system, the complement cascade acts as a first-line defense against pathogens, and upon activation, its amplification loop ensures a strong, rapid, and sustained response. Excessive activation, however, can lead to host tissue damage and cause complement-associated diseases like AMD. AMD patients present with aberrant activation of the alternative pathway, especially in ocular tissues but also on a systemic level. Here, we review the latest findings of complement activation in AMD, and we will discuss in vivo observations made in human tissue, cellular models, the potential synergy of different AMD-associated pathways, and conclude on current clinical trials and the future outlook.
引用
收藏
页码:279 / 297
页数:19
相关论文
共 154 条
[41]   An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD) [J].
Fritsche, Lars G. ;
Lauer, Nadine ;
Hartmann, Andrea ;
Stippa, Selina ;
Keilhauer, Claudia N. ;
Oppermann, Martin ;
Pandey, Manoj K. ;
Koehl, Joerg ;
Zipfel, Peter F. ;
Weber, Bernhard H. F. ;
Skerka, Christine .
HUMAN MOLECULAR GENETICS, 2010, 19 (23) :4694-4704
[42]   Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD) [J].
Garcia-Onrubia, Luis ;
Javier Valentin-Bravo, Fco ;
Coco-Martin, Rosa M. ;
Gonzalez-Sarmiento, Rogelio ;
Carlos Pastor, J. ;
Usategui-Martin, Ricardo ;
Pastor-Idoate, Salvador .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (16) :1-32
[43]   The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment [J].
Geerlings, Maartje J. ;
de Jong, Eiko K. ;
den Hollander, Anneke I. .
MOLECULAR IMMUNOLOGY, 2017, 84 :65-76
[44]   The Functional Effect of Rare Variants in Complement Genes on C3b Degradation in Patients With Age-Related Macular Degeneration [J].
Geerlings, Maartje J. ;
Kremlitzka, Mariann ;
Bakker, Bjorn ;
Nilsson, Sara C. ;
Saksens, Nicole T. ;
Lechanteur, Yara T. ;
Pauper, Marc ;
Corominas, Jordi ;
Fauser, Sascha ;
Hoyng, Carel B. ;
Blom, Anna M. ;
de Jong, Eiko K. ;
den Hollander, Anneke I. .
JAMA OPHTHALMOLOGY, 2017, 135 (01) :39-46
[45]   Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration [J].
Golestaneh, Nady ;
Chu, Yi ;
Cheng, Shuk Kei ;
Cao, Hong ;
Poliakov, Eugenia ;
Berinstein, Daniel M. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2016, 14
[46]   Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions [J].
Gong, Jie ;
Cai, Hui ;
Noggle, Scott ;
Paull, Daniel ;
Rizzolo, Lawrence J. ;
Del Priore, Lucian, V ;
Fields, Mark A. .
STEM CELLS TRANSLATIONAL MEDICINE, 2020, 9 (03) :364-376
[47]   Complement Factor H Binds to Human Serum Apolipoprotein E and Mediates Complement Regulation on High Density Lipoprotein Particles [J].
Haapasalo, Karita ;
van Kessel, Kok ;
Nissila, Eija ;
Metso, Jari ;
Johansson, Tiira ;
Miettinen, Sini ;
Varjosalo, Markku ;
Kirveskari, Juha ;
Kuusela, Pentti ;
Chroni, Angelika ;
Jauhiainen, Matti ;
van Strijp, Jos ;
Jokiranta, T. Sakari .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (48) :28977-28987
[48]   Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration:: Characterization, ethnic distribution and evolutionary implications [J].
Hageman, Gregory S. ;
Hancox, Lisa S. ;
Taiber, Andrew J. ;
Gehrs, Karen M. ;
Anderson, Don H. ;
Johnson, Lincoln V. ;
Radeke, Monte J. ;
Kavanagh, David ;
Richards, Anna ;
Atkinson, John ;
Meri, Seppo ;
Bergeron, Julie ;
Zernant, Jana ;
Merriam, Joanna ;
Gold, Bert ;
Allikmets, Rando ;
Dean, Michael .
ANNALS OF MEDICINE, 2006, 38 (08) :592-604
[49]   A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration [J].
Hageman, GS ;
Anderson, DH ;
Johnson, LV ;
Hancox, LS ;
Taiber, AJ ;
Hardisty, LI ;
Hageman, JL ;
Stockman, HA ;
Borchardt, JD ;
Gehrs, KM ;
Smith, RJH ;
Silvestri, G ;
Russell, SR ;
Klaver, CCW ;
Barbazetto, I ;
Chang, S ;
Yannuzzi, LA ;
Barile, GR ;
Merriam, JC ;
Smith, RT ;
Olsh, AK ;
Bergeron, J ;
Zernant, J ;
Merriam, JE ;
Gold, B ;
Dean, M ;
Allikmets, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (20) :7227-7232
[50]   Complement factor H variant increases the risk of age-related macular degeneration [J].
Haines, JL ;
Hauser, MA ;
Schmidt, S ;
Scott, WK ;
Olson, LM ;
Gallins, P ;
Spencer, KL ;
Kwan, SY ;
Noureddine, M ;
Gilbert, JR ;
Schnetz-Boutaud, N ;
Agarwal, A ;
Postel, EA ;
Pericak-Vance, MA .
SCIENCE, 2005, 308 (5720) :419-421