2020
DOI: 10.3390/ijms21186647
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Abstract: Impaired cargo trafficking and the aggregation of intracellular macromolecules are key features of neurodegeneration, and a hallmark of aged as well as diseased retinal pigment epithelial (RPE) cells in the eye. Here, photoreceptor outer segments (POS), which are internalized daily by RPE cells, were modified by UV-irradiation to create oxidatively modified POS (OxPOS). Oxidative modification was quantified by a protein carbonyl content assay. Human ARPE-19 cells were synchronously pulsed with POS or OxPOS to … Show more

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Cited by 7 publications
(10 citation statements)
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References 82 publications
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“…The phenomenon of processing photoreceptor outer segments as part of the daily photoreceptor renewal is unique to RPE, whereby the distal 10% of OS are internalised every 24 h by RPE cells and degraded in the phagosome or autophagy-dependent lysosomal pathways [ 33 ]. The high photo-oxidative environment of the retina as well as defects in cargo processing have been shown to increase the proteolytic burden of RPE cells and contribute to retinopathy [ 4 , 34 , 35 , 36 ]. The age-related accumulation of lipofuscin within RPE, which fills ~20% of the cytoplasm by the eighth decade of life, places a further burden on cellular stress [ 37 , 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…The phenomenon of processing photoreceptor outer segments as part of the daily photoreceptor renewal is unique to RPE, whereby the distal 10% of OS are internalised every 24 h by RPE cells and degraded in the phagosome or autophagy-dependent lysosomal pathways [ 33 ]. The high photo-oxidative environment of the retina as well as defects in cargo processing have been shown to increase the proteolytic burden of RPE cells and contribute to retinopathy [ 4 , 34 , 35 , 36 ]. The age-related accumulation of lipofuscin within RPE, which fills ~20% of the cytoplasm by the eighth decade of life, places a further burden on cellular stress [ 37 , 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…These results confirmed that AFGs have resulted from the fusion of lysosomes to form phagolysosomes and further suggest that CTSD is consumed within AFGs while LAMP1 is retained at the surface of the granules. A recent study followed the fate of POS and oxidatively modified POS (oxPOS) in ARPE-19 cells for 72 h and found that POS were sequentially trafficking to LAMP1 and LAMP2 as reported here but in that study the use of fluorescently-labelled POS prevented the analysis of formation of AFGs 32,33,38 . In post-mortem RPE derived from AMD patients, enlarged and annular LAMP1-positive compartments were observed 39 , which could represent AFGs even though AF was not studied.…”
Section: Discussionmentioning
confidence: 64%
“…Several reports have also shown LC3 colocalization with internalized fluorescently-labelled POS 32,33,38 , as LC3-associated phagocytosis contributes . CC-BY-ND 4.0 International license perpetuity.…”
Section: Discussionmentioning
confidence: 88%
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