Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration

Shen, Shichen; Kapphahn, Rebecca J.; Zhang, Ming; Qian, Shuo; Montezuma, Sandra R.; Shang, Peng; Ferrington, Deborah A.; Qu, Jun

doi:10.3390/ijms24043252

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Moreover, RPE from AMD retinas exhibits upregulation of two important antioxidant enzymes, glutathione peroxidases (GPXs): extracellular GPX3 and mitochondrial isoform of GPX4, which catalyse the reduction of hydrogen peroxide and lipid hydroperoxides by glutathione [517].…”

Section: Current Evidence For Increased Oxidative Stress and Oxidativ...mentioning

confidence: 99%

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Różanowska

2023

Antioxidants

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Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage, which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested to be more sensitive and specific for imaging spectral characteristics of lipofuscin fluorescence.

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Section: Current Evidence For Increased Oxidative Stress and Oxidativ...mentioning

confidence: 99%

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Różanowska

2023

Antioxidants

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“…Finally, the role of oxidative stress in the progression of AMD is underscored by the results of two large clinical trials Age-Related Eye Disease Study (AREDS) and AREDS2 showing that patients with moderate AMD receiving a mixture of antioxidants including vitamin C, vitamin E, zinc and carotenoids were at a smaller risk of progression to advanced AMD, especially if their dietary intake of these antioxidants was low [417][418][419][420].…”

Section: Current Evidence For Increased Oxidative Stress and Oxidativ...mentioning

confidence: 99%

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Różanowska¹

2023

Preprint

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Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

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“…In a proteomic study, it was found that the expression of ATP synthase subunit in RPE was reduced in patients with AMD. The ATP synthase complex is involved in maintaining mitochondrial morphology and mitochondrial membrane potential, and reduced expression of ATP synthase subunits in AMD may lead to defects in key mitochondrial functions [ 99 , 107 ]. Increased PAPR2 expression, decreased AMPK activity, and overactivation of the mTOR pathway were also observed in AMD RPE cells compared to normal RPEs.…”

Section: Roles Of Rpe Cell Phagocytosis and Autophagy In The Developm...mentioning

confidence: 99%

The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy

Zheng

Zhao

2023

Biomolecules

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Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to AMD development and progression. Hence, characterizing the roles of RPE cell phagocytosis and autophagy in the pathogenesis of AMD can inform the development of potential therapeutic targets to prevent irreversible RPE and photoreceptor cell death, thus protecting against AMD.

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Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration

Cited by 6 publications

References 35 publications

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy

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