Lipofuscin Granule Bisretinoid Oxidation in the Human Retinal Pigment Epithelium forms Cytotoxic Carbonyls

Yakovleva, M. A.; Донцов, А. Е.; Трофимова, Н. Н.; Сакина, Н. Л.; Кононихин, А. С.; Aybush, Arseniy V.; Гулин, А. А.; Feldman, T. B.; Оstrovsky, М. А.

doi:10.3390/ijms23010222

Cited by 14 publications

(24 citation statements)

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“…In earlier in vitro experiments [ 38 ], we demonstrated that BisRets-OX, which are formed when LGs are irradiated with visible light, have both hydrophilic and amphiphilic properties, allowing their diffusion through the LG membrane into the RPE cell cytoplasm. It was established that these products contain cytotoxic carbonyls, which can modify cellular proteins and lipids [ 41 ].…”

Section: Resultsmentioning

confidence: 97%

“…Thus, this experiment showed that a significant cytotoxic effect was observed not immediately after irradiation of the samples, but after some time. This suggests that, indeed, for cytotoxic hydrophilic and amphiphilic BisRets-OX [ 38 ], time is needed for the diffusion from LGs into the cytoplasm of the RPE cell and the manifestation of a damaging effect on cell structures.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings that BisRets-OX are TBA-active and have the potential to release LGs [ 38 ] allowed us to assume that they can damage RPE cellular organelles and macromolecules in the dark [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…Our prior in vitro experiments [ 38 ] have demonstrated that BisRets-OX have hydrophilic and amphiphilic properties and are thiobarbituric acid (TBA)-active. Therefore, almost all detectable BisRet-OX species can potentially be released from LGs.…”

Section: Introductionmentioning

confidence: 99%

“…The present research aimed to study the dark toxic effect of LGs on RPE cells after irradiation with visible light when the level of BisRet-OX-containing active carbonyls was increased [ 38 ]. The experiments were performed using LGs obtained from human cadaveric eyes without pathology and the ARPE-19 cell culture.…”

Section: Introductionmentioning

confidence: 99%

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Lipofuscin granules from retinal pigment epithelium (RPE) cells contain bisretinoid fluorophores, which are photosensitizers and are phototoxic to cells. In the presence of oxygen, bisretinoids are oxidized to form various products, containing aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that bisretinoid oxidation and degradation products have both hydrophilic and amphiphilic properties, allowing their diffusion through the lipofuscin granule membrane into the RPE cell cytoplasm, and are thiobarbituric acid (TBA)-active. The purpose of the present study was to determine if these products exhibit a toxic effect to the RPE cell also in the absence of light. The experiments were performed using the lipofuscin-fed ARPE-19 cell culture. The RPE cell viability analysis was performed with the use of flow cytofluorimetry and laser scanning confocal microscopy. The results obtained indicated that the cell viability of the lipofuscin-fed ARPE-19 sample was clearly reduced not immediately after visible light irradiation for 18 h, but after 4 days maintaining in the dark. Consequently, we could conclude that bisretinoid oxidation products have a damaging effect on the RPE cell in the dark and can be considered as an aggravating factor in age-related macular degeneration progression.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%