Oxidative stress and dysfunctional intracellular traffic linked to an unhealthy diet results in impaired cargo transport in the Retinal Pigment Epithelium (RPE)
Oxidative stress and dysfunctional intracellular traffic linked to an unhealthy diet results in impaired cargo transport in the Retinal Pigment Epithelium (RPE)
Scope: oxidative stress and dysregulated intracellular trafficking are associated with an unhealthy diet which underlies pathology. Here, we sought to study these effects on photoreceptor outer segment (POS) trafficking in the Retinal Pigment Epithelium (RPE), a major pathway of disease underlying irreversible sight-loss.
Methods and results: POS trafficking was studied in ARPE-19 cells using an algorithm-based quantification of confocal-immunofluorescence data supported by ultrastructural studies. We show 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 revealed that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appeared limited to POS-containing vesicles, suggesting a cargo-specific effect.
Conclusions: our 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. Our 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. This article is protected by copyright. All rights reserved.
cargo trafficking, oxidative stress, phagosome and autophagy-lysosomal pathways, retinal pigment epithelium (RPE)
Keeling, Eloise
3207bbdb-d391-44af-8abc-a60c08dce45b
Chatelet, David
6371fd7a-e274-4738-9ccb-3dd4dab32928
Johnston, David
b41163c9-b9d2-425c-af99-2a357204014e
Page, Anton
3b346d6a-855c-4838-a609-5eb40257e7c6
Tumbarello, David
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
August 2019
Keeling, Eloise
3207bbdb-d391-44af-8abc-a60c08dce45b
Chatelet, David
6371fd7a-e274-4738-9ccb-3dd4dab32928
Johnston, David
b41163c9-b9d2-425c-af99-2a357204014e
Page, Anton
3b346d6a-855c-4838-a609-5eb40257e7c6
Tumbarello, David
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Keeling, Eloise, Chatelet, David, Johnston, David, Page, Anton, Tumbarello, David, Lotery, Andrew and Ratnayaka, J. Arjuna
(2019)
Oxidative stress and dysfunctional intracellular traffic linked to an unhealthy diet results in impaired cargo transport in the Retinal Pigment Epithelium (RPE).
Molecular Nutrition & Food Research, 63 (15), [1800951].
(doi:10.1002/mnfr.201800951).
Abstract
Scope: oxidative stress and dysregulated intracellular trafficking are associated with an unhealthy diet which underlies pathology. Here, we sought to study these effects on photoreceptor outer segment (POS) trafficking in the Retinal Pigment Epithelium (RPE), a major pathway of disease underlying irreversible sight-loss.
Methods and results: POS trafficking was studied in ARPE-19 cells using an algorithm-based quantification of confocal-immunofluorescence data supported by ultrastructural studies. We show 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 revealed that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appeared limited to POS-containing vesicles, suggesting a cargo-specific effect.
Conclusions: our 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. Our 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. This article is protected by copyright. All rights reserved.
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Accepted/In Press date: 28 February 2019
e-pub ahead of print date: 5 March 2019
Published date: August 2019
Keywords:
cargo trafficking, oxidative stress, phagosome and autophagy-lysosomal pathways, retinal pigment epithelium (RPE)
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Local EPrints ID: 429999
URI: http://eprints.soton.ac.uk/id/eprint/429999
ISSN: 1613-4133
PURE UUID: e26bf045-ec7d-407a-94d7-fd9ff126aee3
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Date deposited: 09 Apr 2019 16:30
Last modified: 06 Jun 2024 04:08
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Author:
Eloise Keeling
Author:
David Chatelet
Author:
David Johnston
Author:
Anton Page
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