{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:02:29Z","timestamp":1777503749256,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pathogenesis of age-related macular degeneration (AMD) remains elusive, despite numerous research studies. Therefore, we aimed to investigate the changes of plasma and IgG-specific N-glycosylation across the disease severity spectrum. We examined 2835 subjects from the 10.001 Dalmatians project, originating from the isolated Croatian islands of Vis and Kor\u010dula. All subjects were classified into four groups, namely (i) bilateral AMD, (ii) unilateral AMD, (iii) early-onset drusen, and (iv) controls. We analysed plasma and IgG N-glycans measured by HPLC and their association with retinal fundus photographs. There were 106 (3.7%) detected cases of AMD; 66 of them were bilateral. In addition, 45 (0.9%) subjects were recorded as having early-onset retinal drusen. We detected several interesting differences across the analysed groups, suggesting that N-glycans can be used as a biomarker for AMD. Multivariate analysis suggested a significant decrease in the immunomodulatory bi-antennary glycan structures in unilateral AMD (adjusted odds ratio 0.43 (95% confidence interval 0.22\u20130.79)). We also detected a substantial increase in the pro-inflammatory tetra-antennary plasma glycans in bilateral AMD (7.90 (2.94\u201320.95)). Notably, some of these associations were not identified in the aggregated analysis, where all three disease stages were collapsed into a single category, suggesting the need for better-refined phenotypes and the use of disease severity stages in the analysis of more complex diseases. Age-related macular degeneration progression is characterised by the complex interplay of various mechanisms, some of which can be detected by measuring plasma and IgG N-glycans. As opposed to a simple case-control study, more advanced and refined study designs are needed to understand the pathogenesis of complex diseases.<\/jats:p>","DOI":"10.3390\/molecules27061774","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"1774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6482-3925","authenticated-orcid":false,"given":"Ivona","family":"Bu\u0107an","sequence":"first","affiliation":[{"name":"Clinical Hospital Centre Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"\u0160kunca Herman","sequence":"additional","affiliation":[{"name":"Clinical Hospital Centre Sisters of Mercy, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Jeron\u010di\u0107 Tomi\u0107","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Gornik","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Genos Ltd., 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoran","family":"Vatavuk","sequence":"additional","affiliation":[{"name":"Clinical Hospital Centre Sisters of Mercy, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kajo","family":"Bu\u0107an","sequence":"additional","affiliation":[{"name":"Clinical Hospital Centre Split, 21000 Split, Croatia"},{"name":"Department of Ophthalmology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordan","family":"Lauc","sequence":"additional","affiliation":[{"name":"Genos Ltd., 10000 Zagreb, Croatia"},{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-1862","authenticated-orcid":false,"given":"Ozren","family":"Pola\u0161ek","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Algebra LAB, Algebra University College, Ilica 242, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1038\/srep04347","article-title":"Changes in IgG and total plasma protein glycomes in acute systemic inflammation","volume":"4","author":"Novokmet","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1021\/pr800737u","article-title":"Variability, heritability and environmental determinants of human plasma N-glycome","volume":"8","author":"Polasek","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/978-3-030-70115-4_17","article-title":"Glycosylation and Aging","volume":"1325","author":"Kavur","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Miura, Y., Hashii, N., Tsumoto, H., Takakura, D., Ohta, Y., Abe, Y., Arai, Y., Kawasaki, N., Hirose, N., and Endo, T. (2015). Change in N-Glycosylation of Plasma Proteins in Japanese Semisupercentenarians. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142645"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/gerona\/glt190","article-title":"Glycans are a novel biomarker of chronological and biological ages","volume":"69","author":"Menni","year":"2014","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrc3982","article-title":"Glycosylation in cancer: Mechanisms and clinical implications","volume":"15","author":"Pinho","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1002\/pmic.200800163","article-title":"Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation","volume":"8","author":"Arnold","year":"2008","journal-title":"Proteomics"},{"key":"ref_8","first-page":"2390","article-title":"Serum glycoprotein-derived N- and O-linked glycans as cancer biomarkers","volume":"6","author":"Lan","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1038\/s41598-018-26805-7","article-title":"Plasma N-glycans in colorectal cancer risk","volume":"8","author":"Doherty","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","first-page":"3002","article-title":"Screening and diagnosis of colorectal cancer and advanced adenoma by Bionic Glycome method and machine learning","volume":"11","author":"Pan","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jchromb.2007.03.003","article-title":"Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients","volume":"853","author":"Nakagawa","year":"2007","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pan.2015.11.002","article-title":"Alteration of serum N-glycan profile in patients with autoimmune pancreatitis","volume":"16","author":"Tomoda","year":"2016","journal-title":"Pancreatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1177\/2050640620916027","article-title":"Immunoglobulin G subtypes-1 and 2 differentiate immunoglobulin G4-associated sclerosing cholangitis from primary sclerosing cholangitis","volume":"8","author":"Vujasinovic","year":"2020","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0009-8981(02)00427-8","article-title":"Altered glycosylation of alpha1-acid glycoprotein in patients with inflammation and diabetes mellitus","volume":"329","author":"Higai","year":"2003","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/s12967-018-1695-0","article-title":"N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease","volume":"16","author":"Dilber","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/glycob\/cwz068","article-title":"A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function","volume":"30","author":"Yamaguchi","year":"2020","journal-title":"Glycobiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13075-017-1389-7","article-title":"IgG Fc galactosylation predicts response to methotrexate in early rheumatoid arthritis","volume":"19","author":"Hensvold","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1089\/omi.2019.0032","article-title":"Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for Common Chronic Diseases","volume":"23","author":"Liu","year":"2019","journal-title":"Omics A J. Integr. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eaax0301","DOI":"10.1126\/sciadv.aax0301","article-title":"Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases","volume":"6","author":"Tsepilov","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Low, S.W.Y., Connor, T.B., Kassem, I.S., Costakos, D.M., and Chaurasia, S.S. (2021). Small Leucine-Rich Proteoglycans (SLRPs) in the Retina. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147293"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-94-007-7893-1_4","article-title":"Proteoglycans and diseases of soft tissues","volume":"802","author":"Halper","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1167\/iovs.13-13783","article-title":"Determination of dynamic changes in the nature and biosynthesis of glycome of wt and rd1 mice retinae by lectin microarray analysis","volume":"55","author":"Ahuja","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"D\u00f6rschmann, P., and Klettner, A. (2020). Fucoidans as Potential Therapeutics for Age-Related Macular Degeneration-Current Evidence from In Vitro Research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239272"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1111\/febs.15006","article-title":"NA3 glycan: A potential therapy for retinal pigment epithelial deficiency","volume":"286","author":"Chintalapudi","year":"2019","journal-title":"FEBS J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1208\/s12248-014-9563-1","article-title":"Novel endogenous glycan therapy for retinal diseases: Safety, in vitro stability, ocular pharmacokinetic modeling, and biodistribution","volume":"16","author":"Swaminathan","year":"2014","journal-title":"AAPS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13601","DOI":"10.1074\/jbc.RA119.012305","article-title":"High-density lipoproteins are a potential therapeutic target for age-related macular degeneration","volume":"295","author":"Kelly","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1038\/s41598-020-59244-4","article-title":"Dysregulated metabolic pathways in age-related macular degeneration","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.survophthal.2017.05.003","article-title":"Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration","volume":"63","author":"Kersten","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2174\/1389202915666140516204512","article-title":"Using current data to define new approach in age related macular degeneration: Need to accelerate translational research","volume":"15","author":"Anand","year":"2014","journal-title":"Curr. Genom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1007\/s00018-021-03796-9","article-title":"The complement system in age-related macular degeneration","volume":"78","author":"Armento","year":"2021","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/1120672121998900","article-title":"Analysis of association of risk factors for age-related macular degeneration","volume":"32","author":"Bucan","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.preteyeres.2009.06.001","article-title":"Para-inflammation in the aging retina","volume":"28","author":"Xu","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2010.03.006","article-title":"Inflammation 2010: New adventures of an old flame","volume":"140","author":"Medzhitov","year":"2010","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/IIO.0000000000000073","article-title":"Inflammatory Mechanisms of Age-related Macular Degeneration","volume":"55","author":"Knickelbein","year":"2015","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"546786","DOI":"10.1155\/2012\/546786","article-title":"Mechanism of inflammation in age-related macular degeneration","volume":"2012","author":"Parmeggiani","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0039-6257(99)00072-7","article-title":"Drusen in age-related macular degeneration: Pathogenesis, natural course, and laser photocoagulation-induced regression","volume":"44","author":"Abdelsalam","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0161-6420(97)30322-4","article-title":"Characterization of drusen-associated glycoconjugates","volume":"104","author":"Mullins","year":"1997","journal-title":"Ophthalmology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1136\/bjophthalmol-2016-309729","article-title":"Five-year progression of unilateral age-related macular degeneration to bilateral involvement: The Three Continent AMD Consortium report","volume":"101","author":"Joachim","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.3389\/fimmu.2019.03024","article-title":"Minimal B Cell Extrinsic IgG Glycan Modifications of Pro- and Anti-Inflammatory IgG Preparations in vivo","volume":"10","author":"Schaffert","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nm0395-237","article-title":"Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein","volume":"1","author":"Malhotra","year":"1995","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10611","DOI":"10.1073\/pnas.1513456112","article-title":"A common glycan structure on immunoglobulin G for enhancement of effector functions","volume":"112","author":"Lin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2017.11.041","article-title":"Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease","volume":"172","author":"Pagan","year":"2018","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1089\/omi.2019.0004","article-title":"Hyperuricemia is Associated with Immunoglobulin G N-Glycosylation: A Community-Based Study of Glycan Biomarkers","volume":"23","author":"Hou","year":"2019","journal-title":"OMICS"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s12967-018-1616-2","article-title":"The changes of immunoglobulin G N-glycosylation in blood lipids and dyslipidaemia","volume":"16","author":"Liu","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_46","first-page":"688","article-title":"Aging enhances lymphocyte cytokine defects after injury","volume":"17","author":"Plackett","year":"2003","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.preteyeres.2013.07.003","article-title":"Aging is not a disease: Distinguishing age-related macular degeneration from aging","volume":"37","author":"Ardeljan","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.ajo.2013.08.003","article-title":"Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration","volume":"156","author":"Cao","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1001\/jamaophthalmol.2013.7671","article-title":"Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: The Beaver Dam Eye Study","volume":"132","author":"Klein","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104293","DOI":"10.1016\/j.jprot.2021.104293","article-title":"High-throughput rat immunoglobulin G N-glycosylation profiling revealed subclass-specific changes associated with chronic stress","volume":"245","author":"Habazin","year":"2021","journal-title":"J. Proteom."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cvetko, A., Kifer, D., Gornik, O., Klari\u0107, L., Visser, E., Lauc, G., Wilson, J.F., and \u0160tambuk, T. (2020). Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100410"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Miyahara, K., Nouso, K., Saito, S., Hiraoka, S., Harada, K., Takahashi, S., Morimoto, Y., Kobayashi, S., Ikeda, F., and Miyake, Y. (2013). Serum glycan markers for evaluation of disease activity and prediction of clinical course in patients with ulcerative colitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074861"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/0896-8411(91)90173-A","article-title":"Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy","volume":"4","author":"Rook","year":"1991","journal-title":"J. Autoimmun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/03009742.2019.1641615","article-title":"Immunoglobulin G galactosylation levels are decreased in systemic sclerosis patients and differ according to disease subclassification","volume":"49","author":"Liu","year":"2020","journal-title":"Scand. J. Rheumatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.thromres.2018.04.005","article-title":"Structural changes of fibrinogen as a consequence of cirrhosis","volume":"166","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1111\/all.14775","article-title":"Tear N-glycomics in vernal and atopic keratoconjunctivitis","volume":"76","author":"Messina","year":"2021","journal-title":"Allergy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/glycob\/cwu108","article-title":"Glycomic characterisation of basal tears and changes with diabetes and diabetic retinopathy","volume":"25","author":"Kautto","year":"2015","journal-title":"Glycobiology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3325\/cmj.2009.50.4","article-title":"\u201c10001 Dalmatians:\u201d Croatia launches its national biobank","volume":"50","author":"Rudan","year":"2009","journal-title":"Croat. Med. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/hmg\/ddl473","article-title":"Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits","volume":"16","author":"Campbell","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41467-017-00031-7","article-title":"Large meta-analysis of genome-wide association studies identifies five loci for lean body mass","volume":"8","author":"Zillikens","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3325\/cmj.2011.52.262","article-title":"Ethical aspects of human biobanks: A systematic review","volume":"52","author":"Budimir","year":"2011","journal-title":"Croat. Med. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0039-6257(05)80092-X","article-title":"An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group","volume":"39","author":"Bird","year":"1995","journal-title":"Surv. Ophthalmol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1774\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:06Z","timestamp":1760135646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/6\/1774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":62,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["molecules27061774"],"URL":"https:\/\/doi.org\/10.3390\/molecules27061774","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}