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

2021 ◽  
Vol 23 (1) ◽  
pp. 222
Author(s):  
Marina Yakovleva ◽  
Alexander Dontsov ◽  
Natalia Trofimova ◽  
Natalia Sakina ◽  
Alexey Kononikhin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Oxidation Products ◽  
Lipofuscin Granule ◽  
Age Related ◽  
Aldehydes And Ketones ◽  
Lipofuscin Granules

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–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 oxidation products are a likely aggravating factor in the pathogenesis of AMD.

scholarly journals Comparative study of oxidant properties of oxidized and unoxidized bisretinoids of lipofuscine granules in the retinal pigment epithelium of human eye

2019 ◽  
pp. 66-71
Author(s):  
М.А. Яковлева ◽  
Н.Л. Сакина ◽  
И.Б. Кольчугина ◽  
П.М. Арбуханова ◽  
С.А. Борзенок ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Retinal Pigment Epithelium ◽  
Comparative Study ◽  
Degradation Products ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Lipofuscin Granules

Актуальность. Недавно нами было показано, что при возрастной макулярной дегенерации сетчатки наблюдается повышенное содержание продуктов фотоокисления и фотодеградации бисретиноидов по сравнению с нормой. Поэтому на сегодняшний день вопрос о фототоксичности этих продуктов становится актуальным для решения проблемы поиска путей лечения и профилактики патологии. Цель. Провести сравнительное исследование фотосенсибилизирующего действия N-ретинилиден-N-ретинилэтаноламина (А2Е) и продуктов его фотоокисления и фотодеградации на индуцированную видимым светом пероксидацию липидов фоторецепторных мембран. Материалы и методы. При помощи метода высокоэффективной жидкостной хроматографии были получены отдельные фракции неокисленных и окисленных бисретиноидов в хлороформном экстракте липофусциновых гранул из ретинального пигментного эпителия кадаверных глаз. Результаты. Проведено сравнительное исследование фототоксических свойств неокисленных и окисленных бисретиноидов липофусциновых гранул из клеток ретинального пигментного эпителия глаза человека на пероксидацию липидов наружных сегментов фоторецепторных клеток. Выводы. Окисленные бисретиноиды липофусциновых гранул менее фототоксичны по сравнению с их неокисленными формами. Background. Recently we have shown that age-related macular degeneration is associated with higher than normal levels of bisretinoid photo-oxidation and photo-degradation products. Therefore, the issue of their phototoxicity currently becomes relevant for finding ways to treat and prevent this pathology. Aim. To conduct a comparative study of the photosensitizing effect of N-retinylidene-N-retinylethanolamine (A2E) and its photooxidation and photodegradation products on light-induced lipid peroxidation in photoreceptor membranes. Materials and methods. Using high-performance liquid chromatography fractions of unoxidized and oxidized bisretinoids were isolated in the chloroform extract of lipofuscin granules from the retinal pigment epithelium of cadaver eyes. Results. The study compared phototoxic effects of unoxidized and oxidized bisretinoids of lipofuscin granules from human retinal pigment epithelial cells on lipid peroxidation in rod outer segments. Conclusions. Oxidized bisretinoids of lipofuscin granules are less phototoxic compared to their unoxidized forms.

scholarly journals Fluorescence characteristics of lipofuscin fluorophores from human retinal pigment epithelium

2020 ◽  
Vol 19 (7) ◽  
pp. 920-930 ◽  
Author(s):  
Marina A. Yakovleva ◽  
Alexandra Sh. Radchenko ◽  
Tatiana B. Feldman ◽  
Alexey A. Kostyukov ◽  
Patimat M. Arbukhanova ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Human Retinal Pigment Epithelium ◽  
Age Related ◽  
Fluorescence Characteristics ◽  
Lipofuscin Granules

Lipofuscin granules accumulate in the retinal pigment epithelium (RPE) with age, especially in patients with visual diseases, including progressive age-related macular degeneration (AMD).

In Vivo Multimodal Retinal Imaging Correlates With Granular-specific Changes in the Organelles of Retinal Pigment Epithelium of a Murine Model of Stargardt Disease

2021 ◽  
Author(s):  
Ratheesh K. Meleppat ◽  
Kaitryn E. Ronning ◽  
Sarah J. Karlen ◽  
Marie E. Burns ◽  
Edward N. Pugh ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Stargardt Disease ◽  
Rpe Cells ◽  
Age Related ◽  
Lipofuscin Granules

Abstract Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of granular pigmented organelles found in the retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin granules in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study the disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4-/- mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess the melanosome density in vivo, whereas the AF images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize the lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased number of melanosomes in the RPE of Abca4-/- mice and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo in the two mouse strains.

scholarly journals In vivo multimodal retinal imaging of disease-related pigmentary changes in retinal pigment epithelium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ratheesh K. Meleppat ◽  
Kaitryn E. Ronning ◽  
Sarah J. Karlen ◽  
Marie E. Burns ◽  
Edward N. Pugh ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Stargardt Disease ◽  
Rpe Cells ◽  
Age Related ◽  
Lipofuscin Granules

AbstractMelanosomes, lipofuscin, and melanolipofuscin are the three principal types of pigmented granules found in retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4−/− mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess melanosome density in vivo, whereas the autofluorescence (AF) images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased concentration of melanosomes in the RPE of Abca4−/− mice, and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo between the two mouse strains.

scholarly journals 4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Age Related ◽  
Tnf Α ◽  
Cox 2

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

scholarly journals Retinal Pigment Epithelium Expressed Toll-like Receptors and Their Potential Role in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8387
Author(s):  
Alexa Klettner ◽  
Johann Roider
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Current Status ◽  
Toll Like Receptors ◽  
Cell Degeneration ◽  
Age Related

(1) Background: Inflammation is a major pathomechanism in the development and progression of age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) may contribute to retinal inflammation via activation of its Toll-like receptors (TLR). TLR are pattern recognition receptors that detect the pathogen- or danger-associated molecular pattern. The involvement of TLR activation in AMD is so far not understood. (2) Methods: We performed a systematic literature research, consulting the National Library of Medicine (PubMed). (3) Results: We identified 106 studies, of which 54 were included in this review. Based on these studies, the current status of TLR in AMD, the effects of TLR in RPE activation and of the interaction of TLR activated RPE with monocytic cells are given, and the potential of TLR activation in RPE as part of the AMD development is discussed. (4) Conclusion: The activation of TLR2, -3, and -4 induces a profound pro-inflammatory response in the RPE that may contribute to (long-term) inflammation by induction of pro-inflammatory cytokines, reducing RPE function and causing RPE cell degeneration, thereby potentially constantly providing new TLR ligands, which could perpetuate and, in the long run, exacerbate the inflammatory response, which may contribute to AMD development. Furthermore, the combined activation of RPE and microglia may exacerbate neurotoxic effects.

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