title: Time-of-flight secondary ion mass spectrometry to assess spatial distribution of A2E and its oxidized forms within lipofuscin granules isolated from human retinal pigment epithelium.
abstract: Lipofuscin granules accumulate in the cells of retinal pigment epithelium with age, particularly in patients with hereditary diseases. These granules are heterogeneous, being composed of mixtures of proteins and lipids, including more than 21 different fluorescent compounds. Bisretinoids and their photo-oxidation and photodegradation products represent the main source of lipofuscin fluorescence and exhibit phototoxic properties. This study used time-of-flight secondary ion mass spectrometry (ToF-SIMS) with in-depth probing to assess the depth distribution of N-retinylidene-N-retinylethanolamine (A2E) and its singly and doubly oxidized forms (A2E-ox and A2E-2ox, respectively) within lipofuscin granules and in their surface layer (lipid membrane). ToF-SIMS showed that A2E and its oxidized forms were uniformly distributed throughout lipofuscin granules but were not present at the membrane surface layer. This finding is important for understanding the process involved in the formation of lipofuscin granules and in their toxicity.
authors: Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119334, Russia.
authors: Marina A
authors: MA
authors: Yakovleva
authors: Semenov Institute of Chemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119991, Russia.|Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow, 119991, Russia.
authors: Alexander A
authors: AA
authors: Gulin
authors: Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119334, Russia. feldmantb@mail.ru.|Department of Molecular Physiology, Biological Faculty, Lomonosov Moscow State University, Leninskie Gory1, Moscow, 119991, Russia. feldmantb@mail.ru.
authors: Tatiana B
authors: TB
authors: Feldman
authors: Department of Molecular Physiology, Biological Faculty, Lomonosov Moscow State University, Leninskie Gory1, Moscow, 119991, Russia.
authors: Yuriy C
authors: YC
authors: Bel'skich
authors: Sv. Fyodorov Eye Microsurgery Complex, Beskudnikovsky bld. 59a, Moscow, 127486, Russia.
authors: Patimat M
authors: PM
authors: Arbukhanova
authors: Semenov Institute of Chemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119991, Russia.
authors: Artem A
authors: AA
authors: Astaf'ev
authors: Semenov Institute of Chemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119991, Russia.|Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow, 119991, Russia.
authors: Victor A
authors: VA
authors: Nadtochenko
authors: Sv. Fyodorov Eye Microsurgery Complex, Beskudnikovsky bld. 59a, Moscow, 127486, Russia.
authors: Sergey A
authors: SA
authors: Borzenok
authors: Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin st. 4, Moscow, 119334, Russia.|Department of Molecular Physiology, Biological Faculty, Lomonosov Moscow State University, Leninskie Gory1, Moscow, 119991, Russia.
authors: Mikhail A
authors: MA
authors: Ostrovsky
mesh_terms: D000368:Aged; D006801:Humans; D008062:Lipofuscin / Q000737:chemistry*; D008875:Middle Aged; D010084:Oxidation-Reduction; D055213:Retinal Pigment Epithelium / Q000737:chemistry* / Q000166:cytology; D012176:Retinoids / Q000032:analysis*; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D008062:Lipofuscin; D012176:Retinoids
keywords: Bisretinoid fluorophores; Lipofuscin granule; Retinal pigment epithelium; Time-of-flight secondary ion mass spectrometry