{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:45:17Z","timestamp":1792453517068,"version":"4.5.0"},"reference-count":163,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch\u2019s membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch\u2019s membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/biom15081059","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:44:45Z","timestamp":1753184685000},"page":"1059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch\u2019s Membrane Pathology and Age-Related Macular Degeneration (AMD)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-4908","authenticated-orcid":false,"given":"Ali A.","family":"Hussain","sequence":"first","affiliation":[{"name":"Rescue, Repair and Regeneration Theme, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6863-4850","authenticated-orcid":false,"given":"Yunhee","family":"Lee","sequence":"additional","affiliation":[{"name":"AltRegen Co., Ltd., 1201, Byoksan Digital Valley 5-cha, Beotkkot-ro, Seoul 08513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1111\/febs.15776","article-title":"A guide to the composition and functions of the extracellular matrix","volume":"288","author":"Karamanos","year":"2021","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-9133-4_1","article-title":"The complex interplay between extracellular matrix and cells in tissues","volume":"Volume 1952","author":"Manou","year":"2019","journal-title":"The Extracellular Matrix: Methods and Protocols"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Karamanos, N.K. (2012). Extracellular matrix: A functional scaffold. Extracellular Matrix: Pathobiology and Signalling, Walter de Gruyter GmbH & Co KG.","DOI":"10.1515\/9783110258776"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1111\/febs.14818","article-title":"The extracellular matrix as a multitasking player in disease","volume":"286","author":"Theocharis","year":"2019","journal-title":"FEBS J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100038","DOI":"10.1016\/j.mbplus.2020.100038","article-title":"Complexity of matrix phenotypes","volume":"6","author":"Iozzo","year":"2020","journal-title":"Matrix Biol. Plus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9152","DOI":"10.1021\/acs.chemrev.8b00354","article-title":"Proteoglycan chemical diversity drives multifunctional cell regulation and therapeutics","volume":"118","author":"Karamanos","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a005108","DOI":"10.1101\/cshperspect.a005108","article-title":"Extracellular \u20ac matrix: Functions in the nervous system","volume":"3","author":"Barros","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3389\/fphys.2020.00253","article-title":"Skeletal muscle extracellular matrix\u2014What do we know about its composition, regulation, and physiological roles? A narrative review","volume":"11","author":"Csapo","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10542","DOI":"10.1038\/s41598-019-46896-0","article-title":"Extracellular matrix composition of connective tissues: A systematic review and meta-analysis","volume":"9","author":"McKee","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1136\/bjo.79.10.944","article-title":"Preparation of Bruch\u2019s membrane and analysis of the age-related changes in the structural collagens","volume":"79","author":"Karwatowski","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1474-9726.2011.00752.x","article-title":"Glycation-altered proteolysis as a pathobiologic mechanism that links glycemic index, aging, and age-related macular disease","volume":"11","author":"Uchiki","year":"2012","journal-title":"Aging Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.exer.2010.02.013","article-title":"Macromolecular diffusion characteristics of ageing human Bruch\u2019s membrane: Implications for age-related macular degeneration (AMD)","volume":"90","author":"Hussain","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s000180050495","article-title":"Matrix metalloproteinases in tumour invasion","volume":"57","author":"Johansson","year":"2000","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1096\/fasebj.12.12.1075","article-title":"Matrix metalloproteinases: Structures, evolution, and diversification","volume":"12","author":"Massova","year":"1998","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1096\/fasebj.5.8.1850705","article-title":"Matrix metalloproteinases and their inhibitors in connective tissue remodelling","volume":"5","author":"Woessner","year":"1991","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1111\/febs.15701","article-title":"Multifunctional intracellular matrix metalloproteinases: Implications in disease","volume":"288","author":"Bassiouni","year":"2021","journal-title":"FEBS J."},{"key":"ref_17","first-page":"1003","article-title":"Age-related macular degeneration and changes in the extracellular matrix","volume":"20","author":"Romaniuk","year":"2014","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_18","first-page":"465","article-title":"Structure, function, and pathology of Bruch\u2019s membrane","volume":"Volume 1","author":"Ryan","year":"2012","journal-title":"Retina"},{"key":"ref_19","first-page":"443","article-title":"The relationships of age changes in retinal pigment epithelium and Bruch\u2019s membrane","volume":"40","author":"Okubo","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","first-page":"775","article-title":"Increase in the advanced glycation end-product pentosidine in Bruch\u2019s membrane with age","volume":"40","author":"Handa","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1001\/archopht.1994.01090150132035","article-title":"Analysis of lipid deposits extracted from human macular and peripheral Bruch\u2019s membrane","volume":"112","author":"Holz","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ajo.2003.11.069","article-title":"The epidemiology of age-related macular degeneration","volume":"137","author":"Klein","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archopht.122.4.564","article-title":"Prevalence of age-related macular degeneration in the United States","volume":"122","author":"Friedman","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_24","first-page":"353","article-title":"Age-related macular degeneration (AMD): Pathogenesis and therapy","volume":"58","author":"Nowak","year":"2006","journal-title":"Pharmacol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv. Ophthalmol."},{"key":"ref_26","first-page":"32","article-title":"Oxidative damage and age-related macular degeneration","volume":"5","author":"Winkler","year":"1999","journal-title":"Mol. Vis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.preteyeres.2009.11.004","article-title":"Retinal light damage: Mechanisms and protection","volume":"29","author":"Organisciak","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"8269","DOI":"10.1073\/pnas.0708714104","article-title":"The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model","volume":"104","author":"Kim","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF02536034","article-title":"Mechanisms of Free Radical Oxidation of Unsaturated Lipids","volume":"30","author":"Porter","year":"1995","journal-title":"Lipids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0891-5849(91)90192-6","article-title":"Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes","volume":"11","author":"Esterbauer","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29354","DOI":"10.1074\/jbc.M910191199","article-title":"The biosynthesis of A2E, a fluorophore of ageing retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer membrane","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16182","DOI":"10.1073\/pnas.0604255103","article-title":"Complement activation by photo-oxidation 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_35","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_36","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1096\/fj.03-0289fje","article-title":"Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2E may contribute to the pathogenesis of age-related macular degeneration","volume":"18","author":"Bergmann","year":"2004","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1194\/jlr.M007518","article-title":"Long-chain and very long chain polyunsaturated fatty acids in ocular ageing and age-related macular degeneration","volume":"51","author":"Liu","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7548","DOI":"10.1016\/j.bmc.2009.09.009","article-title":"Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: Mediators of age-related macular degeneration","volume":"17","author":"Lu","year":"2009","journal-title":"Biorg. Med. Chem."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1167\/iovs.11-8545","article-title":"Natural history of age-related retinal lesions that precede AMD in mice fed high or low glycemic index diets","volume":"53","author":"Weikel","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7275","DOI":"10.1073\/pnas.0913112107","article-title":"Structural characterization of bisretinid 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_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. Ret. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1755-1536-1-5","article-title":"Redox mechanisms in hepatic chronic wound healing and fibrogenesis","volume":"1","author":"Novo","year":"2008","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1167\/iovs.02-0496","article-title":"Quick freeze\/deep-etch visualization of age-related lipid accumulation in Bruch\u2019s membrane","volume":"44","author":"Ruberti","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18207","DOI":"10.1074\/jbc.M300457200","article-title":"A2E-epoxides damage DNA in retinal pigment epithelial cells\u2014Vitamin E and other antioxidants inhibit A2E-epoxide formation","volume":"278","author":"Sparrow","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1167\/iovs.06-0549","article-title":"Effects of lipid peroxidation-related protein modifications on RPR lysosomal functions and POS phagocytosis","volume":"48","author":"Kaemmerer","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","first-page":"772","article-title":"Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration","volume":"13","author":"Suzuki","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_48","first-page":"195","article-title":"Aging human RPE\u2014Morphometric analysis of macular, equatorial, and peripheral cells","volume":"25","author":"Hilderbrand","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: An approach to the aetiology of age-related macular degeneration","volume":"99","author":"Crabb","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"42027","DOI":"10.1074\/jbc.M305460200","article-title":"Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration","volume":"278","author":"Gu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.exer.2006.12.015","article-title":"High concentration of zinc in sub-retinal pigment epithelial deposits","volume":"84","author":"Lengyel","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_53","first-page":"2970","article-title":"The effect of age on the macromolecular permeability of human Bruch\u2019s membrane","volume":"42","author":"Moore","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1167\/iovs.04-0074","article-title":"RPE cels internalize low-density lipoprotein (LDL) and xidized LDL (oxLDL) in large quantities in vitro and in vivo","volume":"45","author":"Gordiyenko","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","first-page":"1306","article-title":"Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process","volume":"12","author":"Tserentsoodol","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1136\/bjo.2005.086579","article-title":"An experimental study of the elastic properties of the human Bruch\u2019s membrane-choroid complex: Relevance to ageing","volume":"90","author":"Ugarte","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101037","DOI":"10.1016\/j.preteyeres.2021.101037","article-title":"Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life","volume":"89","author":"Lewandowski","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1009599","DOI":"10.3389\/fnins.2022.1009599","article-title":"Exploring the pathogenesis of age-related macular degeneration: A review of the interplay between retinal pigment epithelium dysfunction and the innate immune system","volume":"16","author":"Wong","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0002-9394(99)00032-X","article-title":"Antioxidant enzymes in the macular pigment epithelium of eyes with neovascular age-related macular degeneration","volume":"127","author":"Frank","year":"1999","journal-title":"Am. J. Ophthalmol."},{"key":"ref_60","first-page":"1909","article-title":"Mitochondrial superoxide dismutase in mature and developing human retinal pigment epithelium","volume":"33","author":"Oliver","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_61","first-page":"3661","article-title":"Protection of retinal pigment epithelium from oxidative injury by glutathione and precursors","volume":"34","author":"Sternberg","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","first-page":"516","article-title":"Oxygen distribution in the Macaque retina","volume":"34","author":"Ahmed","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/jnr.23583","article-title":"Glucose, lactate and shuttling of metabolites in vertebrate retinas","volume":"93","author":"Hurley","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_64","first-page":"1560","article-title":"Mechanisms of subretinal fluid resorption in the cat eye","volume":"27","author":"Negi","year":"1986","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","first-page":"3513","article-title":"Ion transport mechanisms in native human retinal pigment epithelium","volume":"33","author":"Quinn","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1994.sp020081","article-title":"K+ and Cl\u2212 transport mechanisms in bovine pigment epithelium that could modulate subretinal space, volume and composition","volume":"475","author":"Bialek","year":"1994","journal-title":"J. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/BF02174060","article-title":"Resorption of subretinal fluid by transepithelial flow of the retinal pigment epithelium","volume":"223","author":"Chihara","year":"1985","journal-title":"Graefe\u2032s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_68","first-page":"1564","article-title":"Quantitative estimation of metabolic transport of subretinal fluid","volume":"27","author":"Negi","year":"1986","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","first-page":"1776","article-title":"Measurement of the volume flow and hydraulic conductivity across the isolated dog retinal pigment epithelium","volume":"28","author":"Tsuboi","year":"1987","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","first-page":"1747","article-title":"Effect of plasma osmolality and intraocular pressure on fluid movement across the blood-retinal barrier","volume":"29","author":"Tsuboi","year":"1988","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","unstructured":"Ioseliani, O.R. (2004). Chapter IV. Transport characteristics of ageing human Bruch\u2019s membrane: Implications for AMD. Focus on Macular Degeneration Research, Nova Science Publishers, Inc."},{"key":"ref_72","first-page":"674","article-title":"Retinal pigment epithelial detachments in the elderly","volume":"105","author":"Bird","year":"1986","journal-title":"Trans. Ophthalmol. Soc. UK"},{"key":"ref_73","first-page":"1290","article-title":"Age-related variation in the hydraulic conductivity of Bruch\u2019s membrane","volume":"36","author":"Moore","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1006\/exer.1996.0066","article-title":"Hydrodynamics of ageing Bruch\u2019s membrane: Implications for macular disease","volume":"62","author":"Starita","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1364\/JOSAA.19.000166","article-title":"Age related alterations in the diffusional transport of amino acids across the human Bruch\u2019s-choroid complex","volume":"19","author":"Hussain","year":"2002","journal-title":"J. Opt. Soc. Am. A"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8403","DOI":"10.1167\/iovs.15-16936","article-title":"Modulating the transport characteristics of Bruch\u2019s membrane with steroidal glycosides and its relevance to age-related macular degeneration (AMD)","volume":"56","author":"Lee","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ophtha.2015.09.041","article-title":"Delayed rod-mediated dark adaptation is a functional biomarker for incident early age-related macular degeneration","volume":"123","author":"Owsley","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.exer.2010.01.014","article-title":"Age-related accumulation of 3-nitrotyrosine and nitro-A2E in human Bruch\u2019s membrane","volume":"90","author":"Murdaugh","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1242\/dev.124.8.1519","article-title":"Matrix metalloproteinases regulate morphogenesis, migration and remodelling of epithelium, tongue skeletal muscle and cartilage in the mandibular arch","volume":"124","author":"Chin","year":"1997","journal-title":"Development"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1749-6632.1999.tb07671.x","article-title":"Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity","volume":"878","author":"Pilcher","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1515\/BC.2004.058","article-title":"Protease degradomics: Mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors","volume":"385","author":"Overall","year":"2004","journal-title":"Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1074\/jbc.M111.314609","article-title":"Biochemical analysis of matrix metalloproteinase activation of chemokines CCL15 and CCL23 and increased glycosaminoglycan binding of CCL16","volume":"287","author":"Starr","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/onc.2014.22","article-title":"MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy","volume":"34","author":"Hsu","year":"2015","journal-title":"Oncogene"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1007\/s00018-019-03178-2","article-title":"Metalloproteinases and their tissue inhibitors in Alzheimer\u2019s disease and other neurodegenerative disorders","volume":"76","author":"Rivera","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1074\/jbc.272.4.2446","article-title":"Membrane-type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules","volume":"272","author":"Ohuchi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0092-8674(00)81768-7","article-title":"Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins","volume":"95","author":"Hiraoka","year":"1998","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0092-8674(00)80064-1","article-title":"MT1-MMPdeficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover","volume":"99","author":"Holmbeck","year":"1999","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.semcdb.2007.06.008","article-title":"Membrane type 1-matrix metalloproteinase: Substrate diversity in pericellular proteolysis","volume":"19","author":"Barbolina","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/bies.950140705","article-title":"The matrix degrading metalloproteinases","volume":"14","author":"Matrisian","year":"1992","journal-title":"Bioessays"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1177\/10454411930040020401","article-title":"Matrix metalloproteinases: A review","volume":"4","author":"Moore","year":"1993","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"100775","DOI":"10.1016\/j.preteyeres.2019.100775","article-title":"Understanding the complexity of the matrix metalloproteinase system and its relevance to age-related diseases: Age-related macular degeneration and Alzheimer\u2019s disease","volume":"74","author":"Hussain","year":"2020","journal-title":"Prog. Ret. Eye Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/S0021-9258(18)52334-6","article-title":"Mutational analysis of the transin (rat stromelysin) autoinhibitory region demonstrates a role for residues surrounding the \u201ccysteine switch\u201d","volume":"266","author":"Park","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.matbio.2015.02.007","article-title":"Extracellular regulation of metalloproteinases","volume":"44","author":"Yamamoto","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1074\/jbc.M110931200","article-title":"Substrate binding of gelatinase B induces its enzymatic activity in the presence of intact propeptide","volume":"277","author":"Bannikov","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"27924","DOI":"10.1074\/jbc.M109.035147","article-title":"Control of promatrilysin (MMP7) activation and substrate specific activity by sulphated glycosaminoglycans","volume":"284","author":"Ra","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1021\/bi702260q","article-title":"Beta-hematin interaction with the hemopexin domain of gelatinase B\/MMP9 provokes autocatalytic processing of the propeptide, thereby priming activation by MMP3","volume":"17","author":"Geurts","year":"2008","journal-title":"Biochemistry"},{"key":"ref_97","first-page":"2676","article-title":"Age-dependent variation in metalloproteinase activity of isolated human Bruch\u2019s membrane and choroid","volume":"4","author":"Guo","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1076\/ceyr.16.2.102.5086","article-title":"Discreet expression and distribution pattern of TIMP-3 in the human retina and choroid","volume":"16","author":"Vranka","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_99","first-page":"3179","article-title":"Cytokines cause cultured retinal pigment epithelium cells to secrete metalloproteinases and to contract collagen gels","volume":"34","author":"Hunt","year":"1993","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_100","first-page":"2520","article-title":"Expression of matrix metalloproteinases and inhibitor by human retinal pigment epithelium","volume":"31","author":"Alexander","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1006\/exer.1997.0287","article-title":"Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in the retinal pigment epithelium and interphotoreceptor matrix: Vectorial secretion and regulation","volume":"64","author":"Padgett","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_102","first-page":"323","article-title":"Tissue inhibitor of metalloproteinases-3 is a component of Bruch\u2019s membrane of the eye","volume":"150","author":"Fariss","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Madzharova, E., Kastl, P., Sabino, F., and Keller, U. (2019). Post-Translational Modification-Dependent Activity of Matrix Metalloproteinases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123077"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"102355","DOI":"10.1016\/j.sbi.2022.102355","article-title":"Glycosaminoglycan interaction networks and databases","volume":"74","author":"Perez","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.csbj.2017.03.004","article-title":"Protein post-translational modifications: In silico prediction tools and molecular modeling","volume":"15","author":"Audagnotto","year":"2017","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1093\/jxb\/ery295","article-title":"Orchestrating the proteome with post-translational modifications","volume":"69","author":"Spoel","year":"2018","journal-title":"J. Exp. Bot."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1074\/mcp.M113.031310","article-title":"Proteolytic Post-translational Modification of Proteins: Proteomic Tools and Methodology","volume":"12","author":"Rogers","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/msb.201304521","article-title":"Evolution and functional cross-talk of protein post-translational modifications","volume":"9","author":"Beltrao","year":"2013","journal-title":"Mol. Syst. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cyto.2018.02.026","article-title":"How post-translational modifications influence the biological activity of chemokines","volume":"109","author":"Vanheule","year":"2018","journal-title":"Cytokine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.3389\/fmicb.2018.02661","article-title":"Post-translational modification control of HBV biological processes","volume":"9","author":"Yang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"19238","DOI":"10.1074\/jbc.M117.782300","article-title":"Post-translational modifications clustering within proteolytic domains decrease mutant huntingtin toxicity","volume":"292","author":"Arbez","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/jcmm.12181","article-title":"Heterogeneity of serum gelatinases MMP-2 and MMP-9 isoforms and charge variants","volume":"18","author":"Rossano","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nmeth.2371","article-title":"Zymography methods for visualizing hydrolytic enzymes","volume":"10","author":"Vandooren","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1126\/science.1073634","article-title":"S-nitrosylation of matrix metalloproteinases: Signalling pathway to neuronal cell death","volume":"297","author":"Gu","year":"2002","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1096\/fj.06-7938com","article-title":"Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation","volume":"21","author":"Sariahmetoglu","year":"2007","journal-title":"FASEB J."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Jacob-Ferreira, A.L., Kondo, M.Y., Baral, P.K., James, M.N.G., Holt, A., Fan, X., and Schulz, R. (2013). Phosphorylation Status of 72 kDa MMP-2 Determines Its Structure and Activity in Response to Peroxynitrite. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071794"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cardfail.2007.04.010","article-title":"Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)","volume":"13","author":"Bonnema","year":"2007","journal-title":"J. Card. Fail."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/j.1471-4159.1992.tb09352.x","article-title":"Characterization of neutral proteases from Alzheimer-affected and control brain specimens: Identification of calcium-dependent metalloproteinases from the hippocampus","volume":"58","author":"Backstrom","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1046\/j.1471-4159.1997.68041606.x","article-title":"Matrix metalloproteinases in dog brains exhibiting Alzheimer-like characteristics","volume":"68","author":"Lim","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"37258","DOI":"10.1074\/jbc.M106089200","article-title":"The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B\/MMP9 and neutrophil-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL","volume":"276","author":"Yan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.3892\/ol.2015.3132","article-title":"Failure of matrix metalloproteinase-9 dimer induction by phorbol 12-myristate 13-acetate in normal human cell lines","volume":"9","author":"Roomi","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1167\/iovs.09-4259","article-title":"High molecular-weight gelatinase species of human Bruch\u2019s membrane: Compositional analyses and age-related changes","volume":"51","author":"Hussain","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1167\/iovs.10-6678","article-title":"Disturbed matrix metalloproteinase activity of Bruch\u2019s membrane in age-related macular degeneration","volume":"52","author":"Hussain","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1167\/iovs.09-4195","article-title":"Increased sequestration of matrix metalloproteinases in ageing human Bruch\u2019s membrane: Implications for ECM turnover","volume":"51","author":"Kumar","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_125","first-page":"21","article-title":"Disturbed Matrix Metalloproteinases Activity in Age-Related Macular Degeneration","volume":"Volume 1415","author":"LaVail","year":"2023","journal-title":"Bowes Rickman C"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1097\/00001756-199707070-00015","article-title":"Localisation of tissue inhibitor of metalloproteinase-3 in neurodegenerative retinal disease","volume":"8","author":"Jomary","year":"1997","journal-title":"NeuroReport"},{"key":"ref_127","first-page":"2367","article-title":"TIMP-3 in Bruch\u2019s membrane: Changes during aging and in age-related macular degeneration","volume":"40","author":"Kamei","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1167\/iovs.08-2383","article-title":"CTGF is increased in basal deposits and regulates matrix production through the ERK (p42\/p44 mapk) MAPK and the p38 MAPK signalling pathways","volume":"50","author":"Nagai","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.exer.2005.10.005","article-title":"The expression of advanced glycation endproduct receptors in RPE cells associated with basal deposits in human maculas","volume":"82","author":"Yamada","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/ki.1997.455","article-title":"Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility","volume":"52","author":"Mott","year":"1997","journal-title":"Kidney Int."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/0005-2795(71)90226-1","article-title":"Evidence for progressive, age-related structural changes in post-mature human collagen","volume":"23","author":"Hamlin","year":"1971","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1042\/bj1810639","article-title":"Native cross-links in collagen fibrils induce resistance to human synovial collagenase","volume":"181","author":"Vater","year":"1979","journal-title":"Biochem. J."},{"key":"ref_133","first-page":"213","article-title":"Role of the low density lipoprotein receptor-related protein\/\u03b12-macroglobulin receptor in the regulation of protease activity in the extracellular matrix","volume":"16","author":"Stoppelli","year":"2000","journal-title":"Dent. Mater."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Hu, J., Ni, S., Cao, Y., Zhang, T., Wu, T., Yin, X., Lang, Y., Lu, H., and Zhao, C. (2016). The angiogenic effect of microRNA-21 targeting TIMP3 through the regulation of MMP2 and MMP9. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149537"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.omtn.2021.02.021","article-title":"MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening","volume":"24","author":"Schellinger","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"589985","DOI":"10.3389\/fcell.2020.589985","article-title":"The impact of miRNAs in health and disease of retinal pigment epithelium","volume":"8","author":"Intartaglia","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4155\/fmc.11.176","article-title":"miRNAs as potential therapeutic targets for age-related macular degeneration","volume":"4","author":"Wang","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5331","DOI":"10.1074\/jbc.270.10.5331","article-title":"Mechanism of cell surface activation of 72kDa type IV collagenase. Isolation of the activated form of the membrane metalloproteinase","volume":"270","author":"Strongin","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1076\/ceyr.16.9.925.5044","article-title":"Membrane type-1 matrix metalloproteinase in human ocular tissues","volume":"16","author":"Smine","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1074\/jbc.273.2.871","article-title":"The TIMP-2 membrane type I metalloproteinase \u2018receptor\u2019 regulates the concentration and efficient activation of progelatinase A: A kinetic study","volume":"273","author":"Butler","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/sj.eye.6702722x","article-title":"Plasma levels of matrix metalloproteinase-2 and \u20139 (MMP2 and MMP9) in age-related macular degeneration","volume":"22","author":"Chau","year":"2008","journal-title":"Eye"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study Research Group (2001). A randomized, placebo controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol., 119, 1417\u20131436.","DOI":"10.1001\/archopht.119.10.1417"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.ophtha.2013.01.021","article-title":"Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration. AREDS report No. 35","volume":"120","author":"Chew","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Study 2 (AREDS2) Research Group (2013). Lutein + zeaxanthine and omega-3 fatty acids for age-related macular degeneration: The age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA, 309, 2005\u20132015.","DOI":"10.1001\/jama.2013.4997"},{"key":"ref_145","first-page":"CD000253","article-title":"Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration","volume":"7","author":"Evans","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1097\/IAE.0000000000001659","article-title":"Health conditions linked to age-related macular degeneration associated with dark adaptation","volume":"38","author":"Lains","year":"2018","journal-title":"Retina"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.jfo.2019.07.003","article-title":"Geographic atrophy and micronutritional supplements: A complex relationship","volume":"42","author":"Desmettre","year":"2019","journal-title":"J. Fr. Ophthalmol."},{"key":"ref_148","first-page":"458","article-title":"Expression of metalloproteinases from human retinal pigment epithelium cells and their effects on the hydraulic conductivity of Bruch\u2019s membrane","volume":"43","author":"Ahir","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_149","first-page":"1","article-title":"Surface activities of ginseng saponins and their interactions with biomolecules, I. Separations and surface activities of major saponins from fresh ginseng roots","volume":"14","author":"Lee","year":"1981","journal-title":"Korean Biochem. J."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0009-2797(85)90013-4","article-title":"Effects of purified ginseng saponins on multilamellar liposomes","volume":"56","author":"Yu","year":"1985","journal-title":"Chem. Biol. Interact."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.bcp.2013.02.025","article-title":"Lipid raft modulation by Rp1 reverses multidrug resistance via inactivating MDR-1 and Src inhibition","volume":"85","author":"Yun","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.4238\/2014.May.9.2","article-title":"Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway","volume":"13","author":"Qiu","year":"2014","journal-title":"Genet. Mol. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S0161-6420(01)00580-2","article-title":"Delays in rod-mediated dark adaptation in early age-related maculopathy","volume":"108","author":"Owsley","year":"2002","journal-title":"Ophthalmology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1167\/iovs.11-8958","article-title":"Relationship between clinical macular changes and retinal function in age-related macular degeneration","volume":"53","author":"Dimitrov","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/j.ophtha.2015.06.023","article-title":"Impairments in dark adaptation are associated with age-related macular degeneration severity and reticular pseudodrusen","volume":"122","author":"Flamendorf","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"100143","DOI":"10.1016\/j.apjo.2025.100143","article-title":"Triterpenoid saponin-mediated recovery of visual deficits in age-related macular degeneration (AMD): Double-blind, placebo-controlled, randomized clinical trial","volume":"14","author":"Lee","year":"2025","journal-title":"Asia-Pac. J. Ophthalmol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1001\/archopht.1992.01080240126045","article-title":"Response of the retinal pigment epithelium to selective photocoagulation","volume":"110","author":"Roider","year":"1992","journal-title":"Arch. Ophthalmol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/1096-9101(2000)27:5<451::AID-LSM1006>3.0.CO;2-1","article-title":"Origin of RPE cell damage by pulsed laser irradiance in the ns to ms time regime","volume":"27","author":"Brinkmann","year":"2000","journal-title":"Lasers Surg. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/02713680902964892","article-title":"Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT","volume":"34","author":"Framme","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1167\/iovs.11-8585","article-title":"Laser-mediated activation of human retinal pigment epithelial cells and concomitant release of matrix metalloproteinases","volume":"53","author":"Zhang","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.exer.2012.02.011","article-title":"Vectorial release of matrix metalloproteinases (MPs) from porcine RPE-choroid explants following selective retina therapy (SRT): Towards slowing the macular ageing process","volume":"97","author":"Treumer","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/ceo.12247","article-title":"Nano-second laser application in intermediate AMD: 12-month results of fundus appearance and macular function","volume":"42","author":"Guymer","year":"2014","journal-title":"Clin. Expt. Ophthalmol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.ophtha.2018.09.015","article-title":"Subthreshold nanosecond laser intervention in age-related macular degeneration: The LEAD randomized controlled clinical trial","volume":"126","author":"Guymer","year":"2019","journal-title":"Ophthalmology"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1059\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:13:49Z","timestamp":1760033629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":163,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["biom15081059"],"URL":"https:\/\/doi.org\/10.3390\/biom15081059","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}