{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:24:26Z","timestamp":1788020666657,"version":"build-2784847793"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of Russia","award":["075-15-2020-795 (local identifier 13.1902.21.0027"],"award-info":[{"award-number":["075-15-2020-795 (local identifier 13.1902.21.0027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging of the retina is accompanied by a sharp increase in the content of lipofuscin granules and bisretinoid A2E in the cells of the retinal pigment epithelium (RPE) of the human eye. It is known that A2E can have a toxic effect on RPE cells. However, the specific mechanisms of the toxic effect of A2E are poorly understood. We investigated the effect of the products of photooxidative destruction of A2E on the modification of bovine serum albumin (BSA) and hemoglobin from bovine erythrocytes. A2E was irradiated with a blue light-emitting diode (LED) source (450 nm) or full visible light (400\u2013700 nm) of a halogen lamp, and the resulting water-soluble products of photooxidative destruction were investigated for the content of carbonyl compounds by mass spectrometry and reaction with thiobarbituric acid. It has been shown that water-soluble products formed during A2E photooxidation and containing carbonyl compounds cause modification of serum albumin and hemoglobin, measured by an increase in fluorescence intensity at 440\u2013455 nm. The antiglycation agent aminoguanidine inhibited the process of modification of proteins. It is assumed that water-soluble carbonyl products formed as a result of A2E photodestruction led to the formation of modified proteins, activation of the inflammation process, and, as a consequence, to the progression of various senile eye pathologies.<\/jats:p>","DOI":"10.3390\/ijms23031534","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"1534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Water-Soluble Products of Photooxidative Destruction of the Bisretinoid A2E Cause Proteins Modification in the Dark"],"prefix":"10.3390","volume":"23","author":[{"given":"Alexander","family":"Dontsov","sequence":"first","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Yakovleva","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Trofimova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Sakina","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gulin","sequence":"additional","affiliation":[{"name":"N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arseny","family":"Aybush","sequence":"additional","affiliation":[{"name":"N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4532-778X","authenticated-orcid":false,"given":"Fedor","family":"Gostev","sequence":"additional","affiliation":[{"name":"N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Vasin","sequence":"additional","affiliation":[{"name":"N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-056X","authenticated-orcid":false,"given":"Tatiana","family":"Feldman","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"},{"name":"Department of Biology, Lomonosov Moscow State University, Leninskiye Gory 1, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Ostrovsky","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"},{"name":"Department of Biology, Lomonosov Moscow State University, Leninskiye Gory 1, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1001\/archopht.1992.01080130101035","article-title":"The long-term effects of visible light on the eye","volume":"110","author":"Taylor","year":"1992","journal-title":"Arch. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.redox.2013.01.006","article-title":"Lipofuscin: Formation, effects and role of macro autophagy","volume":"1","author":"Hohn","year":"2013","journal-title":"Redox Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/S0891-5849(99)00003-9","article-title":"Retinal pigment epithelium pigment granules stimulate the photo-oxidation of unsaturated fatty acid","volume":"26","author":"Dontsov","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/eye.1995.192","article-title":"Lipofuscin of the retinal pigment epithelium: A review","volume":"9","author":"Kennedy","year":"1995","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1021\/ja953480g","article-title":"Ocular age pigment A2E: An unprecedented pyridinium bisretinoid","volume":"118","author":"Sakai","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/S0960-894X(01)00314-6","article-title":"Fluorescent pigments of the retinal pigment epithelium and age-related macular degeneration","volume":"11","author":"Parish","year":"2001","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1562\/0031-8655(2002)075<0184:TROAIP>2.0.CO;2","article-title":"The role of A2E in prevention or enhancement of light damage in human retinal pigment epithelial cells","volume":"75","author":"Roberts","year":"2002","journal-title":"Photochem. Photobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/1011-1344(93)87085-2","article-title":"Lipofuscin is a photoinducible free radical generator","volume":"19","author":"Boulton","year":"1993","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.exer.2005.01.007","article-title":"RPE lipofuscin and its role in retinal pathobiology","volume":"80","author":"Sparrow","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18825","DOI":"10.1074\/jbc.270.32.18825","article-title":"Blue light-induced reactivity of retinal age pigment","volume":"270","author":"Rozanowska","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_12","first-page":"2303","article-title":"Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin","volume":"41","author":"Schutt","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","first-page":"1981","article-title":"The lipofuscin fluorophore A2E mediates blue light\u2013induced damage to retinal pigmented epithelial cells","volume":"41","author":"Sparrow","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","first-page":"32","article-title":"Oxidative damage and age-related macular degeneration","volume":"5","author":"Winkler","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00418-016-1462-3","article-title":"The high correlation between counts and area fractions of lipofuscin granules, a biomarker of oxidative stress in muscular dystrophies","volume":"146","author":"Nakae","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.exer.2007.02.018","article-title":"Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2)","volume":"85","author":"Bakall","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.1073\/pnas.130110497","article-title":"Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration","volume":"97","author":"Mata","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.exer.2009.07.021","article-title":"Elovl4 5-bp deletion knock-in mouse model for Stargardt-like macular degeneration demonstrates accumulation of ELOVL4 and lipofuscin","volume":"89","author":"Vasireddy","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_19","first-page":"285","article-title":"Multiple A2E treatments lead to melanization of rod outer segment\u2013challenged ARPE-19 cells","volume":"20","author":"Poliakov","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Montenegro, D., Zhao, J., and Sparrow, J.R. (2021). Bisretinoids of the retina: Photo-oxidation, iron-catalyzed oxidation, and disease consequences. Antioxidants, 10.","DOI":"10.3390\/antiox10091382"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"bio058600","DOI":"10.1242\/bio.058600","article-title":"Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration","volume":"10","author":"Zhang","year":"2021","journal-title":"Biol. Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1562\/0031-8655(2003)077<0253:COTAPO>2.0.CO;2","article-title":"Comparison of the aerobic photoreactivity of A2E with its precursor retinal","volume":"77","author":"Pawlak","year":"2003","journal-title":"Photochem. Photobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1074\/mcp.M700525-MCP200","article-title":"Retinal pigment epithelium lipofuscin proteomics","volume":"7","author":"Ng","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1167\/iovs.03-0172","article-title":"Proteins modified by malondialdehyde, 4-hydroxynonenal or advanced glycation end products in lipofuscin of human retinal pigment epithelium","volume":"44","author":"Schutt","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12013-020-00942-1","article-title":"Photoreactivity of Bis-retinoid A2E Complexed with a Model Protein in Selected Model Systems","volume":"78","author":"Furso","year":"2020","journal-title":"Cell Biochem. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27215","DOI":"10.1074\/jbc.M115.680363","article-title":"Correlations between photodegradation of bisretinoid constituents of retina and dicarbonyl adduct deposition","volume":"290","author":"Zhou","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/php.12200","article-title":"A2E mediated photochemical modification to fibronectin and its implications to age related changes in Bruch\u2019s membrane","volume":"90","author":"Thao","year":"2014","journal-title":"Photochem. Photobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17929","DOI":"10.1038\/s41598-018-36322-2","article-title":"Lipofuscin-mediated photodynamic stress induces adverse changes in nanomechanical properties of retinal pigment epithelium cells","volume":"8","author":"Wiktor","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tarau, I.-S., Berlin, A., Curcio, C.A., and Ach, T. (2019). The Cytoskeleton of the Retinal Pigment Epithelium: From Normal Aging to Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143578"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1096\/fj.06-7896com","article-title":"Confocal Raman microscopy can quantify advanced glycation end products (AGE) modifications Bruch\u2019s membrane leading to accurate, nondestructive prediction of ocular aging","volume":"21","author":"Glenn","year":"2007","journal-title":"FASEB J."},{"key":"ref_31","first-page":"4816","article-title":"Multiplex analysis of age-related protein and lipid modifications in human Bruch\u2019s membrane","volume":"24","author":"Beattie","year":"2010","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.exer.2009.03.021","article-title":"Modifications to the basement membrane protein laminin using glycolaldehyde and A2E: A model for aging in Bruch\u2019s membrane","volume":"89","author":"Murdaugh","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1196\/annals.1433.066","article-title":"Advanced glycation as a basis for understanding retinal aging and noninvasive risk prediction","volume":"1126","author":"Pawlak","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.cyto.2013.03.027","article-title":"Parainflammation associated with advanced glycation endproduct stimulation of RPE In Vitro: Implications for age-related degenerative diseases of the eye","volume":"62","author":"Lin","year":"2013","journal-title":"Cytokine"},{"key":"ref_35","first-page":"212","article-title":"Lifestyle and advanced glycation end-products (AGEs) burden: Its relevance to healthy aging","volume":"5","author":"Prasad","year":"2014","journal-title":"Aging Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1016\/j.bbadis.2018.08.036","article-title":"Mechanistic targeting of advanced glycation end-products in age-related diseases","volume":"1864","author":"Rowan","year":"2018","journal-title":"BBA Mol. Basis Dis."},{"key":"ref_37","first-page":"1","article-title":"Chemistry and pathobiology of advanced glycation end products","volume":"131","author":"Schleicher","year":"2001","journal-title":"Contrib. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1002\/mnfr.201500759","article-title":"Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression","volume":"60","author":"Lin","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1134\/S1607672906040089","article-title":"Detection and study of the products of photooxidation of N-retinylidene-N-retinylethanolamine, the fluorophore of lipofuscin granules from retinal pigment epithelium of human donor eyes","volume":"409","author":"Yakovleva","year":"2006","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1134\/S1607672909020112","article-title":"Light-induced release of A2E photooxidation toxic products from lipofuscin granules of human retinal pigment epithelium","volume":"425","author":"Dontsov","year":"2009","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1562\/2006-04-01-RA-864","article-title":"Oxidation of A2E results in the formation of highly reactive aldehydes and ketones","volume":"82","author":"Wang","year":"2006","journal-title":"Photochem. Photobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.preteyeres.2011.12.001","article-title":"The bisretinoids of retinal pigment epithelium","volume":"31","author":"Sparrow","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"012063","DOI":"10.1088\/1742-6596\/1695\/1\/012063","article-title":"Multimodal approach to reveal the effect of light irradiation on chemical composition of lipofuscin granules of human RPE tissues","volume":"1695","author":"Aybush","year":"2020","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39732","DOI":"10.1074\/jbc.M504933200","article-title":"Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin","volume":"280","author":"Jang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7275","DOI":"10.1073\/pnas.0913112107","article-title":"Structural characterization of bisretinoid A2E photocleavage products and implications for age-related macular degeneration","volume":"107","author":"Wu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21837","DOI":"10.1074\/jbc.R700019200","article-title":"Oxidative stress and covalent modification of protein with bioactive aldehydes","volume":"283","author":"Grimsrud","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1016\/j.bmcl.2012.04.130","article-title":"The effects of aminoguanidine on retinopathy in STZ-induced diabetic rats","volume":"22","author":"Luo","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1472-8206.1999.tb00358.x","article-title":"Antioxidant properties of aminoguanidine","volume":"13","author":"Dalloz","year":"1999","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pasten, C., Lozano, M., Rocco, J., Carri\u00f3n, F., Alvarado, C., Liberona, J., Michea, L., and Irarr\u00e1zabal, C.E. (2021). Aminoguanidine Prevents the Oxidative Stress, Inhibiting Elements of Inflammation, Endothelial Activation, Mesenchymal Markers, and Confers a Renoprotective Effect in Renal Ischemia and Reperfusion Injury. Antioxidants, 10.","DOI":"10.3390\/antiox10111724"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2003.08.013","article-title":"Use of aminoguanidine to prevent the formation of advanced glycation end products","volume":"419","author":"Thornalley","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1039\/c5pp00156k","article-title":"Determination of N-retinylidene-N-retinylethanolamine (A2E) levels in central and peripheral areas of human retinal pigment epithelium","volume":"14","author":"Adler","year":"2015","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ruan, Y., Jiang, S., and Gericke, A. (2021). Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031296"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16182","DOI":"10.1073\/pnas.0604255103","article-title":"Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium","volume":"103","author":"Zhou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/187221309787158371","article-title":"Chronic Inflammation and Oxidative Stress as a Major Cause of Age-Related Diseases and Cancer","volume":"3","author":"Khansari","year":"2009","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1006\/exer.2001.1094","article-title":"Complement activation and inflammatory processes in drusen formation and age-related macular degeneration","volume":"73","author":"Johnson","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0002-9394(02)01624-0","article-title":"A role for local inflammation in the formation of drusen in the aging eye","volume":"134","author":"Anderson","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ophtha.2008.09.055","article-title":"Complement component C3 and risk of age-related macular degeneration","volume":"116","author":"Despriet","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1167\/iovs.09-4478","article-title":"Age-Related Macular Degeneration: The Molecular Link between Oxidative Damage, Tissue-Specific Inflammation and Outer Retinal Disease: The Proctor Lecture","volume":"51","author":"Hollyfield","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1007\/s00018-016-2147-8","article-title":"Inflammation and its role in age-related macular degeneration","volume":"73","author":"Kauppinen","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_60","unstructured":"Morgan, B.P., and Harris, C.L. (1999). Complement Regulatory Proteins, Academic Press."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: An approach to the etiology of age-related macular degeneration","volume":"99","author":"Crabb","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1073\/pnas.0501536102","article-title":"A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration","volume":"102","author":"Hageman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-60761-541-5_5","article-title":"Animal models for age-related macular degeneration","volume":"Volume 46","author":"Pang","year":"2010","journal-title":"Animal Models for Retinal Diseases"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm1709","article-title":"Oxidative damage induced inflammation initiates age-related macular degeneration","volume":"14","author":"Hollyfield","year":"2008","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-1-4615-0067-4_11","article-title":"Proteomic approaches to understanding age-related macular degeneration","volume":"533","author":"Hollyfield","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14609","DOI":"10.1073\/pnas.95.25.14609","article-title":"Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium","volume":"95","author":"Parish","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0076-6879(90)86134-H","article-title":"Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal","volume":"186","author":"Esterbauer","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1534\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:15Z","timestamp":1760134215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":68,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031534"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031534","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}