Cis-urocanic acid improves cell viability and suppresses inflammasome activation in human retinal pigment epithelial cells

Eveliina Korhonen; Niina Piippo; Maria Hytti; Kai Kaarniranta; Anu Kauppinen

doi:10.1016/j.bcp.2023.115790

Cis-urocanic acid improves cell viability and suppresses inflammasome activation in human retinal pigment epithelial cells

Biochem Pharmacol. 2023 Oct:216:115790. doi: 10.1016/j.bcp.2023.115790. Epub 2023 Sep 6.

Authors

Eveliina Korhonen¹, Niina Piippo², Maria Hytti³, Kai Kaarniranta⁴, Anu Kauppinen⁵

Affiliations

¹ Immuno-Ophthalmology, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland. Electronic address: eveliina.korhonen@uef.fi.
² Immuno-Ophthalmology, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland.
³ Immuno-Ophthalmology, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, P.O.Box 100, FI-70029 Kuopio, Finland.
⁴ Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, P.O.Box 100, FI-70029 Kuopio, Finland.
⁵ Immuno-Ophthalmology, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland. Electronic address: anu.kauppinen@uef.fi.

PMID: 37683842
DOI: 10.1016/j.bcp.2023.115790

Abstract

Age-related macular degeneration (AMD) is a common eye disease among the elderly, which can result in impaired vision and irreversible loss of vision. The majority of patients suffer from the dry (also known as the atrophic) form of the disease, which is completely lacking an effective treatment. In the present study, we evaluated the potential of cis-urocanic acid (cis-UCA) to protect human ARPE-19 cells from cell damage and inflammasome activation induced by UVB light. Urocanic acid is a molecule normally present in human epidermis. Its cis-form has recently been found to alleviate UVB-induced inflammasome activation in human corneal epithelial cells. Here, we observed that cis-UCA is well-tolerated also by human retinal pigment epithelial (RPE) cells at a concentration of 100 μg/ml. Moreover, cis-UCA was cytoprotective and efficiently diminished the levels of mature IL-1β, IL-18, and cleaved caspase-1 in UVB-irradiated ARPE-19 cells. Interestingly, cis-UCA also reduced DNA damage, whereas its effect against ROS production was negligible. Collectively, cis-UCA protected ARPE-19 cells from UVB-induced phototoxicity and inflammasome activation. This study indicates that due to its beneficial properties of preserving cell viability and preventing inflammation, cis-UCA has potential in drug development of chronic ocular diseases, such as AMD.

Keywords: Anti-inflammatory agent; Cytoprotection; Interleukin-18; Interleukin-1beta; UV light; Urocanic acid.