Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium
Open accessAbstract
Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial (RPE) cells, contribute to the disease process. In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of products resulting from photooxidation of A2E might include a range of fragments that could be recognized by the complement system as “foreign” and that could serve to activate the complement system, leading to low-grade inflammation. To this end, we established an in vitro assay by using human serum as a source of complement, and we measured products of C3 activation by enzyme immunoassay. Accordingly, we found that the C3 split products inactivated C3b (iC3b) and C3a were elevated in serum, overlying ARPE-19 cells that had accumulated A2E and were irradiated to induce A2E photooxidation. Precoating of microtiter plates with two species of oxidized A2E, peroxy-A2E, and furano-A2E, followed by incubation with serum, also activated complement. We suggest that products of the photooxidation of bis-retinoid lipofuscin pigments in RPE cells could serve as a trigger for the complement system, a trigger than would predispose the macula to disease and that, over time, could contribute to chronic inflammation. These findings link four factors that have been posited as being associated with AMD: inflammation, oxidative damage, drusen, and RPE lipofuscin.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A2E and mitochondrial dysfunction are reported to impair RPE phagocytosis and activate the complement system.
“A2E (a by-product of phototransduction, present in lipofuscin) and mitochondrial dysfunction are reported to impair RPE phagocytosis and activate the complement system (156, 178).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [178]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492 · see citing works
(2001) · Archives of Ophthalmology · doi:10.1001/archopht.119.10.1417 · Cited by 3,285 · see citing works
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449 · see citing works
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424 · see citing works
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961 · see citing works
Black, S., Kushner, I., & Samols, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400025200 · Cited by 1,844 · see citing works
Allikmets, R., Singh, N., Sun, H., Shroyer, N. F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., et al. (1997) · Nature Genetics · doi:10.1038/ng0397-236 · Cited by 1,435 · see citing works
Hageman, G. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00010-6 · Cited by 1,265 · see citing works
Drusen proteome analysis: an approach to the etiology of age-related macular degeneration
Crabb, J. W., Miyagi, M., Gu, X., Shadrach, K., West, K. A., Sakaguchi, H., Kamei, M., Hasan, A., Yan, L., Rayborn, M. E., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222551899 · Cited by 1,208 · see citing works
The AMD Genetics Clinical Study Group, Gold, B., Merriam, J. E., Zernant, J., Hancox, L. S., Taiber, A. J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1750 · Cited by 1,075 · see citing works
(2005) · Archives of Ophthalmology · doi:10.1001/archopht.123.11.1484 · Cited by 739 · see citing works
Drusen complement components C3a and C5a promote choroidal neovascularization
Nozaki, M., Raisler, B. J., Sakurai, E., Sarma, J. V., Barnum, S. R., Lambris, J. D., Chen, Y., Zhang, K., Ambati, B. K., Baffi, J. Z., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408835103 · Cited by 650 · see citing works
RPE lipofuscin and its role in retinal pathobiology
Sparrow, J. R., & Boulton, M. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.01.007 · Cited by 644 · see citing works
Self-citationRisk factors associated with age-related macular degeneration
(2000) · Ophthalmology · doi:10.1016/s0161-6420(00)00409-7 · Cited by 633 · see citing works
The Long-term Effects of Visible Light on the Eye
Taylor, H. R. (1992) · Archives of Ophthalmology · doi:10.1001/archopht.1992.01080130101035 · Cited by 568 · see citing works
The Role of Inflammation in the Pathogenesis of Age-related Macular Degeneration
Donoso, L. A., Kim, D. S., Frost, A. T., Callahan, A., & Hageman, G. S. (2006) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2005.12.001 · Cited by 480 · see citing works
Parish, C. A., Hashimoto, M., Nakanishi, K., Dillon, J., & Sparrow, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14609 · Cited by 474 · see citing works
Self-citationMata, N. L., Weng, J., & Travis, G. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130110497 · Cited by 456 · see citing works
Accumulation of cholesterol with age in human Bruch's membrane.
Curcio, C. A., Millican, C. L., Bailey, T. A., & Kruth, H. S. (2001) · PubMed · Cited by 442 · see citing works
Complement activation and protein adsorption by carbon nanotubes
Salvador-Morales, C., Emmanuel Flahaut, B., Sim, E., Sloan, J., HGREEN, M., & Sim, R. B. (2005) · Molecular Immunology · doi:10.1016/j.molimm.2005.02.006 · Cited by 433 · see citing works
Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects.
Delori, F. C., Goger, D. G., & Dorey, C. K. (2001) · PubMed · Cited by 424 · see citing works
Association Between C-Reactive Protein and Age-Related Macular Degeneration
Keenan, T. D. L., & Chew, E. Y. (2017) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2017.2210 · Cited by 378 · see citing works
Association between C-reactive protein and age-related macular degeneration
Seddon, J. M. (2004) · JAMA · doi:10.1001/jama.291.6.704 · Cited by 376 · see citing works
Seddon, J. M. (2005) · Archives of Ophthalmology · doi:10.1001/archopht.123.6.774 · Cited by 354 · see citing works
Dietary intake of antioxidants and risk of age-related macular degeneration
van Leeuwen, R. (2005) · JAMA · doi:10.1001/jama.294.24.3101 · Cited by 345 · see citing works
A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture.
Sparrow, J. R., Parish, C. A., Hashimoto, M., & Nakanishi, K. (1999) · PubMed · Cited by 312 · see citing works
Self-citationComplement Regulatory Proteins
(1999) · Elsevier eBooks · doi:10.1016/b978-0-125-06965-6.x5000-4 · Cited by 294 · see citing works
Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study.
Tomany, S. C., Cruickshanks, K. J., Klein, R., Klein, B. E. K., & Knudtson, M. D. (2004) · PubMed · doi:10.1001/archopht.122.5.750 · Cited by 285 · see citing works
Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE.
Sparrow, J. R., Zhou, J., Ben‐Shabat, S., Vollmer-Snarr, H. R., Itagaki, Y., & Nakanishi, K. (2002) · PubMed · Cited by 284 · see citing works
Self-citationA2E-epoxides Damage DNA in Retinal Pigment Epithelial Cells
Sparrow, J. R., Vollmer-Snarr, H. R., Zhou, J., Jang, Y. P., Steffen Jockusch, B., Itagaki, Y., & Nakanishi, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300457200 · Cited by 280 · see citing works
Self-citationLiu, J., Itagaki, Y., Ben-Shabat, S., Nakanishi, K., & Sparrow, J. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910191199 · Cited by 255 · see citing works
Self-citationSmoking and Age-Related Maculopathy: The Blue Mountains Eye Study
Smith, W. (1996) · Archives of Ophthalmology · doi:10.1001/archopht.1996.01100140716016 · Cited by 255 · see citing works
Dentchev, T., Milam, A. H., Lee, V. M. ‐., Trojanowski, J. Q., & Dunaief, J. L. (2003) · PubMed · Cited by 252 · see citing works
Sunlight and the 5-year incidence of early age-related maculopathy: the beaver dam eye study.
Cruickshanks, K. J., Klein, R., Klein, B. E. K., & Nondahl, D. M. (2001) · PubMed · Cited by 246 · see citing works
Radu, R. A., Han, Y., Bui, T. V., Nusinowitz, S., Bok, D., Lichter, J. B., Widder, K., Travis, G. H., & Mata, N. L. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0820 · Cited by 225 · see citing works
Turro, N. J., & Chow, M. F. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00414a029 · Cited by 222 · see citing works
Biosynthetic Studies of A2E, a Major Fluorophore of Retinal Pigment Epithelial Lipofuscin
Ben-Shabat, S., Parish, C. A., Vollmer, H. R., Itagaki, Y., Fishkin, N., Nakanishi, K., & Sparrow, J. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108981200 · Cited by 214 · see citing works
Self-citationBen‐Shabat, S., Itagaki, Y., Steffen Jockusch, B., Sparrow, J. R., Turro, N. J., & Nakanishi, K. (2002) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20020301)41:5 · Cited by 207 · see citing works
Self-citationOcular Age Pigment “A2-E”: An Unprecedented Pyridinium Bisretinoid
Sakai, N., Decatur, J. D., Nakanishi, K., & Eldred, G. E. (1996) · Journal of the American Chemical Society · doi:10.1021/ja953480g · Cited by 206 · see citing works
Zareparsi, S., Buraczynska, M., Branham, K. E. H., Shah, S., Eng, D., Li, M., Pawar, H., Yashar, B. M., Moroi, S. E., Lichter, P. R., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi154 · Cited by 190 · see citing works
Kim, S. R., Nakanishi, K., Itagaki, Y., & Sparrow, J. R. (2006) · Experimental Eye Research · doi:10.1016/j.exer.2005.10.004 · Cited by 163 · see citing works
Self-citationFishkin, N. E., Sparrow, J. R., Allikmets, R., & Nakanishi, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501266102 · Cited by 146 · see citing works
Self-citationJang, Y. P., Zhou, J., Nakanishi, K., & Sparrow, J. R. (2005) · Photochemistry and Photobiology · doi:10.1562/2004-12-14-ra-402 · Cited by 123 · see citing works
Self-citationJang, Y. P., Matsuda, H., Itagaki, Y., Nakanishi, K., & Sparrow, J. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504933200 · Cited by 119 · see citing works
Self-citationAbnormalities of fundus autofluorescence in central serous retinopathy
von Rückmann, A., Fitzke, F. W., Fan, J., et al. (2002) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(02)01428-9 · Cited by 117 · see citing works
Zhou, J., Cai, B., Jang, Y. P., Pachydaki, S., Schmidt, A. M., & Sparrow, J. R. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2004.11.009 · Cited by 113 · see citing works
Self-citationPossible Protective Role for C-Reactive Protein in Atherogenesis
Bhakdi, S., Torzewski, M., Paprotka, K., Schmitt, S., Barsoom, H., Suriyaphol, P., Han, S., Lackner, K. J., & Husmann, M. (2004) · Circulation · doi:10.1161/01.cir.0000124228.08972.26 · Cited by 113 · see citing works
[1] Complement factor I and cofactors in control of complement system convertase enzymes
Sim, R. B., Day, A. J., Moffatt, B. E., & Fontaine, M. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)23035-l · Cited by 108 · see citing works
Small Molecule RPE65 Antagonists Limit the Visual Cycle and Prevent Lipofuscin Formation
Maiti, P., Kong, J., Kim, S. R., Sparrow, J. R., Allikmets, R. L., & Rando, R. R. (2005) · Biochemistry · doi:10.1021/bi0518545 · Cited by 106 · see citing works
Self-citationInfluence of inflammatory cells and serum on the performance of implantable glucose sensors
Gerritsen, M., Jansen, J. A., Kros, A., Vriezema, D. M., Sommerdijk, N. A. J. M., Nolte, R. J. M., Lutterman, J. A., van Hövell, S. W. F. M., & van der Gaag, A. (2000) · Journal of Biomedical Materials Research · doi:10.1002/1097-4636(200101)54:1 · Cited by 89 · see citing works
Müller-Eberhard, H. J. (1975) · Elsevier eBooks · doi:10.1016/b978-0-12-568401-9.50015-3 · Cited by 81 · see citing works
The photochemical oxidation of A2E results in the formation of a 5,8,5′,8′-bis-furanoid oxide
Dillon, J. P., Wang, Z., Avalle, L. B., & Gaillard, E. R. (2004) · Experimental Eye Research · doi:10.1016/j.exer.2004.06.024 · Cited by 78 · see citing works
Christen, W. G., Ajani, U. A., Glynn, R., Manson, J. E., Schaumberg, D. A., Chew, E. C., Buring, J. E., & Hennekens, C. H. (1999) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009836 · Cited by 76 · see citing works
Jang, Y. P., Zhou, J., Nakanishi, K., et al. (2005) · Photochemistry and Photobiology · doi:10.1562/2004-12-14-ra-402.1 · Cited by 75 · see citing works
Self-citationDaly, J. J., & Kotwal, G. J. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00100-6 · Cited by 39 · see citing works
Zhou, J., Gao, X., Cai, B., & Sparrow, J. R. (2006) · Rejuvenation Research · doi:10.1089/rej.2006.9.256 · Cited by 33 · see citing works
Self-citationTakada, N., Watanabe, M., Yamada, A., et al. (2001) · Journal of Natural Products · doi:10.1021/np0003490 · Cited by 30 · see citing works
Complement activation by oxidatively modified low‐density lipoproteins
Wieland, W., Dorweiler, Bonitz, Lieser, Walev, & Bhakdi (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00548.x · Cited by 27 · see citing works
Hepatocellular bioactivation and cytotoxicity of the synthetic endoperoxide antimalarial arteflene
Maggs, J. L., Bishop, L. P. D., Batty, K. T., et al. (2004) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2003.12.005 · Cited by 12 · see citing works
Noordin, S., Shortkroff, S., Sledge, C. B., et al. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2003.11.057 · Cited by 11 · see citing works
Complement activation by oxidatively modified low‐density lipoproteins
Demacker (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00549.x · Cited by 2 · see citing works
Rother, K. O., Day, N. K., Good, R. A., et al. (1988) · Springer eBooks · doi:10.1007/978-3-642-97038-2_4 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [3]Curcio CA, Millican CL, Bailey T, Kruth HS. Invest Ophthalmol Vis Sci. 2001;42:265–274. [PubMed] [Google Scholar]
- [16]Law SKA, Reid KBM. Complement. Oxford: Oxford Univ Press; 1995. [Google Scholar]
- [27]Delori FC, Goger DG, Dorey CK. Invest Ophthalmol Vis Sci. 2001;42:1855–1866. [PubMed] [Google Scholar]
- [28]Sakai N, Decatur J, Nakanishi K, Eldred GE. J Am Chem Soc. 1996;118:1559–1560. [Google Scholar]
- [34]Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K. Invest Ophthalmol Vis Sci. 2002;43:1222–1227. [PubMed] [Google Scholar]
- [45]Cruickshanks KJ, Klein R, Klein BEK, Nondahl DM. Arch Ophthalmol. 2001;119:246–250. [PubMed] [Google Scholar]
- [56]Dentchev T, Milam AH, Lee VMY, Trojanowski JQ, Dunaief JL. Mol Vis. 2003;9:184–190. [PubMed] [Google Scholar]
- [59]Turro NJ, Chow M-F, Rigaudyo J. J Am Chem Soc. 1981;103:7218–7222. [Google Scholar]
- [60]Sparrow JR, Parish CA, Hashimoto M, Nakanishi K. Invest Ophthalmol Vis Sci. 1999;40:2988–2995. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Anderson, D. H., Radeke, M. J., Gallo, N. B., Chapin, E. A., Johnson, P. T., Curletti, C. R., Hancox, L. S., Hu, J., Ebright, J. N., Malek, G., et al. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.11.003 · Cited by 727 · see citing works
The dynamic nature of Bruch's membrane
Booij, J. C., Baas, D. C., Beisekeeva, J., Gorgels, T. G. M. F., & Bergen, A. A. B. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.08.003 · Cited by 581 · see citing works
Variation in complement factor 3 is associated with risk of age-related macular degeneration
Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., & Seddon, J. M. (2007) · Nature Genetics · doi:10.1038/ng2131 · Cited by 437 · see citing works
Deng, Y., Qiao, L., Du, M., Qu, C., Wan, L., Li, J., & Huang, L. (2022) · Genes & Diseases · doi:10.1016/j.gendis.2021.02.009 · Cited by 411 · see citing works
The bisretinoids of retinal pigment epithelium
Sparrow, J. R., Gregory-Roberts, E., Yamamoto, K., Blonska, A., Ghosh, S. K., Ueda, K., & Zhou, J. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.12.001 · Cited by 392 · see citing works
Self-citationMechanisms of age‐related macular degeneration and therapeutic opportunities
van Lookeren Campagne, M., LeCouter, J., Yaspan, B. L., & Ye, W. (2014) · The Journal of Pathology · doi:10.1002/path.4266 · Cited by 382 · see citing works
Potential of herbs in skin protection from ultraviolet radiation
Korać, R., & Khambholja, K. (2011) · Pharmacognosy Reviews · doi:10.4103/0973-7847.91114 · Cited by 366 · see citing works
Reynolds, R., Hartnett, M. E., Atkinson, J. P., Giclas, P. C., Rosner, B., & Seddon, J. M. (2009) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.09-3928 · Cited by 294 · see citing works
Swaroop, A., Chew, E. Y., Bowes Rickman, C., & Abecasis, G. R. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164350 · Cited by 270 · see citing works
Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice
Maeda, A., Maeda, T., Golczak, M., Chou, S., Desai, A., Hoppel, C. L., Matsuyama, S., & Palczewski, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900322200 · Cited by 248 · see citing works
Ferrington, D. A., Sinha, D., & Kaarniranta, K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.09.002 · Cited by 241 · see citing works
Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction
Coffey, P. J., Gias, C., McDermott, C. J., Lundh, P., Pickering, M. C., Sethi, C., Bird, A., Fitzke, F. W., Maass, A., Chen, L. L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705079104 · Cited by 231 · see citing works
Phospholipid meets all-trans-retinal: the making of RPE bisretinoids
Sparrow, J. R., Wu, Y., Kim, C. Y., & Zhou, J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r000687 · Cited by 193 · see citing works
Self-citationMolday, R. S., Zhong, M., & Quazi, F. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.02.004 · Cited by 182 · see citing works
Retinal Pigment Epithelium Lipofuscin Proteomics
Ng, K.-P., Gugiu, B., Renganathan, K., Davies, M. W., Gu, X., Crabb, J. S., Kim, S. R., Różanowska, M. B., Bonilha, V. L., Rayborn, M. E., et al. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700525-mcp200 · Cited by 162 · see citing works
Self-citationRadu, R. A., Hu, J., Yuan, Q., Welch, D. L., Makshanoff, J., Lloyd, M., McMullen, S., Travis, G. H., & Bok, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.191866 · Cited by 157 · see citing works
Kim, S. R., Jang, Y. P., Jockusch, S., Fishkin, N. E., Turro, N. J., & Sparrow, J. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708714104 · Cited by 145 · see citing works
Self-citationCeruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD
Hadziahmetovic, M., Dentchev, T., Song, Y., Haddad, N., He, X., Hahn, P., Pratico, D., Wen, R., Harris, Z. L., Lambris, J. D., et al. (2008) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.07-1472 · Cited by 121 · see citing works
Li, K., Sacks, S. H., & Zhou, W. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.06.006 · Cited by 98 · see citing works
Metabolism of carotenoids and retinoids related to vision
von Lintig, J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.303990 · Cited by 91 · see citing works
A2E accumulation influences retinal microglial activation and complement regulation
Ma, W., Coon, S., Zhao, L., Fariss, R. N., & Wong, W. T. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.06.010 · Cited by 92 · see citing works
Palczewska, G., Maeda, T., Imanishi, Y., Sun, W., Chen, Y., Williams, D. R., Piston, D. W., Maeda, A., & Palczewski, K. (2010) · Nature Medicine · doi:10.1038/nm.2260 · Cited by 88 · see citing works
Ma, L., Kaufman, Y., Zhang, J., & Washington, I. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.178657 · Cited by 83 · see citing works
Implications of genetic variation in the complement system in age-related macular degeneration
de Jong, S., Gagliardi, G., Garanto, A., de Breuk, A., Lechanteur, Y. T. E., Katti, S., van den Heuvel, L. P., Volokhina, E. B., & den Hollander, A. I. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100952 · Cited by 71 · see citing works
Protective responses to sublytic complement in the retinal pigment epithelium
Tan, L. X., Toops, K. A., & Lakkaraju, A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1523061113 · Cited by 66 · see citing works
Stargardt macular dystrophy and evolving therapies
Hussain, R. M., Ciulla, T. A., Berrocal, A. M., Gregori, N. Z., Flynn, H. W., & Lam, B. L. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1513486 · Cited by 56 · see citing works
Enzymatic Degradation of A2E, a Retinal Pigment Epithelial Lipofuscin Bisretinoid
Wu, Y., Zhou, J., Fishkin, N., Rittmann, B. E., & Sparrow, J. R. (2011) · Journal of the American Chemical Society · doi:10.1021/ja107195u · Cited by 50 · see citing works
Self-citationRadu, R. A., Hu, J., Jiang, Z., & Bok, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.548669 · Cited by 44 · see citing works
Ramo, K., Cashman, S. M., & Kumar-Singh, R. (2008) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.08-2025 · Cited by 38 · see citing works
Bisretinoids of the Retina: Photo-Oxidation, Iron-Catalyzed Oxidation, and Disease Consequences
Kim, H. J., Montenegro, D., Zhao, J., & Sparrow, J. R. (2021) · Antioxidants · doi:10.3390/antiox10091382 · Cited by 35 · see citing works
Self-citationTzoumas, N., Hallam, D., Harris, C. L., Lako, M., Kavanagh, D., & Steel, D. H. W. (2021) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2020.10.008 · Cited by 33 · see citing works
Bruch’s Membrane and the Choroid in Age-Related Macular Degeneration
Edwards, M., & Lutty, G. A. (2021) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-66014-7_4 · Cited by 32 · see citing works
Pyakurel, A., Balmer, D., Saba-El-Leil, M. K., Kizilyaprak, C., Daraspe, J., Humbel, B. M., Voisin, L., Le, Y. Z., von Lintig, J., Meloche, S., et al. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00295-17 · Cited by 20 · see citing works
Bringing age-related macular degeneration into focus
Allikmets, R., & Dean, M. (2008) · Nature Genetics · doi:10.1038/ng0708-820 · Cited by 26 · see citing works
Hu, J., & Bok, D. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60327-325-1_2 · Cited by 24 · see citing works
Qin, T., & Gao, S. (2018) · Journal of Ophthalmology · doi:10.1155/2018/5392432 · Cited by 13 · see citing works
Balmer, D., Bapst-Wicht, L., Pyakurel, A., Emery, M., Nanchen, N., Bochet, C. G., & Roduit, R. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00043 · Cited by 6 · see citing works
- Authors
- Zhou, J., Jang, Y. P., Kim, S. R., & Sparrow, J. R.
- Affiliations
- Departments of *Ophthalmology and
- Columbia University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-10-31
- Volume
- 103
- Issue
- 44
- Pages
- 16182-16187
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1637557
- OpenAlex
- W2009256817
- Cited by
- 358
- References
- 63
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 24 · 2020: 19 · 2019: 10 · 2018: 15 · 2017: 10 · 2016: 11 · 2015: 28 · 2014: 24 · 2013: 27 · 2012: 33
- FWCI
- 17.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (R01EY012951, EY 12951)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- complement activation, A2E, lipofuscin, retinal pigment epithelium, age-related macular degeneration, photooxidation, iC3b, C3a, oxidative damage, drusen, inflammation
- MeSH terms
- Cell Line, Complement C3b, Epithelium, Furans, Humans, Lipofuscin, Oxidation-Reduction, Photochemistry, Pyridinium Compounds, Retinal Pigments, Retinoids, Mass Spectrometry, Molecular Structure, Complement C3a
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
