Keeling E, Chatelet DS, Johnston DA, Page A, Tumbarello DA, Lotery AJ, Ratnayaka JA (2019) Mol Nutr Food Res. 2019 Mar: e1800951. doi: 10.1002/mnfr.201800951. [Epub ahead of print]
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.
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 intracellularcompartments and trafficking in strikingly different ways. These effects appear limited to POS-containing vesicles, suggesting a cargo-specific effect.
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.