{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:50Z","timestamp":1792789550179,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T00:00:00Z","timestamp":1640390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The 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>Age-related macular degeneration (AMD) is the primary cause of central blindness among the elderly. AMD is associated with progressive accumulation of lipofuscin granules in retinal pigment epithelium (RPE) cells. Lipofuscin contains bisretinoid fluorophores, which are photosensitizers and are phototoxic to RPE and neuroretinal cells. In the presence of oxygen, bisretinoids are also oxidized, forming various products, consisting primarily of aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that in AMD, bisretinoid oxidation products are increased in RPE lipofuscin granules. The purpose of the present study was to determine if these products were toxic to cellular structures. The physicochemical characteristics of bisretinoid oxidation products in lipofuscin, which were obtained from healthy donor eyes, were studied. Raman spectroscopy and time-of-flight secondary ion mass spectrometry (ToF\u2013SIMS) analysis identified the presence of free-state aldehydes and ketones within the lipofuscin granules. Together, fluorescence spectroscopy, high-performance liquid chromatography, and mass spectrometry revealed that bisretinoid oxidation products have both hydrophilic and amphiphilic properties, allowing their diffusion through lipofuscin granule membrane into the RPE cell cytoplasm. These products contain cytotoxic carbonyls, which can modify cellular proteins and lipids. Therefore, bisretinoid oxidation products are a likely aggravating factor in the pathogenesis of AMD.<\/jats:p>","DOI":"10.3390\/ijms23010222","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipofuscin Granule Bisretinoid Oxidation in the Human Retinal Pigment Epithelium forms Cytotoxic Carbonyls"],"prefix":"10.3390","volume":"23","author":[{"given":"Marina","family":"Yakovleva","sequence":"first","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Dontsov","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, 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, Kosygin st. 4, 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, Kosygin st. 4, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-3458","authenticated-orcid":false,"given":"Alexey","family":"Kononikhin","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, 119334 Moscow, Russia"},{"name":"Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 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, Kosygin st. 4, bld. 1, 119991 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, Kosygin st. 4, bld. 1, 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, Kosygin st. 4, 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, Kosygin st. 4, 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":[[2021,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1097\/OPX.0000000000000281","article-title":"Age-related macular degeneration: Linking clinical presentation to pathology","volume":"91","author":"Milston","year":"2014","journal-title":"Optom. 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