Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells.

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Research Program for Experimental Ophthalmology, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, Muellner Hauptstrasse 48, 5020, Salzburg, Austria.

Published: October 2020

AI Article Synopsis

  • The retinal pigment epithelium (RPE) relies on autophagy to manage high levels of phagocytosis and oxidative stress, with impaired autophagy linked to disorders like dry age-related macular degeneration (AMD) that currently lack effective treatments.
  • The study focuses on Cysteinyl leukotriene receptor (CysLTR) 1's role in regulating autophagy in ARPE-19 cells, revealing that CysLTR1 influences autophagic activity and is co-localized with β-tubulin III.
  • Results show that inhibiting CysLTR1 with Zafirlukast enhances autophagy and suggests that dysfunction in the leukotriene system could harm RPE functions,

Article Abstract

The retinal pigment epithelium (RPE), which is among the tissues in the body that are exposed to the highest levels of phagocytosis and oxidative stress, is dependent on autophagy function. Impaired autophagy and continuous cellular stress are associated with various disorders, such as dry age-related macular degeneration (AMD), a disease for which effective therapies are lacking. Cysteinyl leukotriene receptor (CysLTR) 1 is a potential modulator of autophagy; thus, the aim of this study was to investigate the role of CysLTR1 in autophagy regulation in the RPE cell line ARPE-19. The polarized ARPE-19 monolayer exhibited expression of CysLTR1, which was colocalized with β-tubulin III. In ARPE-19 cells, autophagic activity was rhythmically regulated and was increased upon CysLTR1 inhibition by Zafirlukast (ZK) treatment. HO affected the proautophagic regulatory effect of ZK treatment depending on whether it was applied simultaneously with or prior to ZK treatment. Furthermore, mRNA levels of genes related to the leukotriene system, autophagy and the unfolded protein response were positively correlated. As CysLTR1 is involved in autophagy regulation under basal and oxidative stress conditions, a dysfunctional leukotriene system could negatively affect RPE functions. Therefore, CysLTR1 is a potential target for new treatment approaches for neurodegenerative disorders, such as AMD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573618PMC
http://dx.doi.org/10.1038/s41598-020-74755-wDOI Listing

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