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

Scientific Reports, 2020 · DOI: 10.1038/s41598-020-74755-w · Published: October 23, 2020

Simple Explanation

The retinal pigment epithelium (RPE) is susceptible to oxidative stress and relies on autophagy. When autophagy is impaired it can lead to disorders such as dry age-related macular degeneration (AMD). Cysteinyl leukotriene receptor (CysLTR) 1 is a potential modulator of autophagy; this study investigates the role of CysLTR1 in autophagy regulation in the RPE cell line ARPE-19. The study found CysLTR1 is involved in autophagy regulation under basal and oxidative stress conditions, and 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.

Study Duration

Not specified

Participants

ARPE-19 cell line

Evidence Level

Level: Not specified, Study type: In vitro cell line study

Key Findings

1
CysLTR1 is expressed in polarized ARPE-19 monolayers and colocalized with β-tubulin III.
2
Autophagic activity in ARPE-19 cells is rhythmically regulated and increases upon CysLTR1 inhibition by Zafirlukast (ZK) treatment.
3
mRNA levels of genes related to the leukotriene system, autophagy, and the unfolded protein response are positively correlated.

Research Summary

This study investigates the role of cysteinyl leukotriene receptor 1 (CysLTR1) in autophagy regulation in retinal pigment epithelial (RPE) cells, which are critical for eye health and affected in diseases like age-related macular degeneration (AMD). The researchers found that CysLTR1 is expressed in RPE cells and that its inhibition increases autophagic activity, a cellular process important for clearing damaged components. Furthermore, they observed rhythmic regulation of autophagy in these cells. The study suggests that CysLTR1 could be a potential therapeutic target for neurodegenerative disorders like AMD, given its involvement in autophagy regulation and the connection between the leukotriene system and RPE function.

Practical Implications

Therapeutic Target

CysLTR1 could serve as a pharmacological target for treating neurodegenerative diseases such as Alzheimer's disease and dry AMD.

Drug Development

Existing CysLTR1 inhibitors like Zafirlukast and Montelukast, used for asthma, might be repurposed or serve as a basis for new AMD treatments.

Further Research

Future studies should investigate the physiological and pathophysiological effects of leukotrienes in AMD-associated cellular systems to develop new therapeutic strategies.

Study Limitations

1
The study uses the ARPE-19 cell line, which may not fully represent in vivo RPE cell behavior.
2
Sex differences cannot be excluded because ARPE-19 cells are of male origin and the CYSLTR1 gene is located on the X chromosome.
3
The precise mechanisms of CysLTR1 involvement in phagocytosis, phagosome transport, and autophagy rhythm require further investigation.

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