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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http://dx.doi.org/10.1038/s41598-020-74755-w | DOI Listing |
Invest Ophthalmol Vis Sci
November 2024
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States.
Purpose: Diabetic macular edema (DME) is the primary cause of vision impairment in diabetic retinopathy (DR) patients. A previous study has shown the efficacy of montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, in a diabetic mouse model. This study aims to understand the CysLTR1 signaling in retinal endothelial cells and the impact of montelukast.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Museum and Institute of Zoology, Polish Academy of Sciences, ul. Twarda 51/55, 00-818 Warszawa, Poland.
Exp Eye Res
November 2024
Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; The MUHC - McGill University Ocular Pathology & Translational Research Laboratory, Montreal, QC, Canada.
J Ocul Pharmacol Ther
December 2024
Department of Ophthalmology, Anatomy & Neurobiology, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Sci Signal
September 2024
Laboratory of Chemical Biology and Signal Transduction, Rockefeller University, New York, NY 10065, USA.
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