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Mol Nutr Food Res. 2019 Aug;63(15):e1800951. doi: 10.1002/mnfr.201800951. Epub 2019 Mar 20.

Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE).

Author information

1
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, SO16 6YD, UK.
2
Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, SO16 6YD, UK.
3
Biological Sciences, Faculty of Natural & Environmental Sciences, University of Southampton, Life Sciences Building 85, SO17 1BJ, UK.
4
Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.

Abstract

SCOPE:

Oxidative stress and dysregulated intracellular trafficking are associated with an unhealthy diet which underlies pathology. Here, these effects on photoreceptor outer segment (POS) trafficking in the retinal pigment epithelium (RPE), a major pathway of disease underlying irreversible sight-loss, are studied.

METHODS AND RESULTS:

POS trafficking is studied in ARPE-19 cells using an algorithm-based quantification of confocal-immunofluorescence data supported by ultrastructural studies. It is shown that although POS are tightly regulated and trafficked via Rab5, Rab7 vesicles, LAMP1/2 lysosomes and LC3b-autophagosomes, there is also a considerable degree of variation and flexibility in this process. Treatment with H2 O2 and bafilomycin A1 reveals that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appear limited to POS-containing vesicles, suggesting a cargo-specific effect.

CONCLUSION:

The findings offer insights into how RPE cells cope with stress, and how mechanisms influencing POS transport/degradation can have different outcomes in the senescent retina. These shed new light on cellular processes underlying retinopathies such as age-related macular degeneration. The discoveries reveal how diet and nutrition can cause fundamental alterations at a cellular level, thus contributing to a better understanding of the diet-disease axis.

KEYWORDS:

cargo trafficking; oxidative stress; phagosome and autophagy-lysosomal pathways; retinal pigment epithelium

PMID:
30835933
DOI:
10.1002/mnfr.201800951

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