Lipofuscin granule bisretinoid oxidation in the human retinal pigment epithelium forms cytotoxic carbonyls

Yakovleva, M.A.; Dontsov, A.E.; Trofimova, N.N.; Sakina, N.L.; Kononikhin, A.S.; Aybush, A.V.; Feldman, T.B.; Ostrovsky, M.A.

Авторы: Yakovleva Marina A., Dontsov Alexander E., Trofimova Natalia N., Sakina Natalia L., Kononikhin Alexey S., Aybush Arseny V., Feldman Tatiana B., Ostrovsky Mikhail A.
Журнал: International Journal of Molecular Sciences
Том: 23
Номер: 1
Год издания: 2022
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 1
Последняя страница: 15
Номер статьи: 222
DOI: 10.3390/ijms23010222
Аннотация: Age-related macular degeneration (AMD) is the primary cause of central blindness amongthe 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 bisretinoidoxidation products in lipofuscin, which were obtained from healthy donor eyes, were studied. Raman spectroscopy and time-of-flight secondary ion mass spectrometry (ToF–SIMS) 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 oxidationproducts are a likely aggravating factor in the pathogenesis of AMD
Добавил в систему: Фельдман Татьяна Борисовна

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Lipofuscin granule bisretinoid oxidation in the human retinal pigment epithelium forms cytotoxic carbonylsстатья

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