Effects of miR-204-5p modulation on PAX6 regulation and corneal inflammation

Congenital aniridia is a rare eye disease characterized by loss of PAX6 protein leading to aniridia-associated keratopathy that significantly reduces vision. The miR-204-5p is a possible regulator of PAX6 function and here we evaluate its effect in multiple in vitro and in vivo models. In vitro, miR...

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Published in:	Scientific reports Vol. 14; no. 1; pp. 26436 - 14
Main Authors:	Abbasi, Mojdeh, Amini, Maryam, Moustardas, Petros, Gutsmiedl, Quirin, Javidjam, Dina, Suiwal, Shweta, Seitz, Berthold, Fries, Fabian N., Dashti, Ava, Rautavaara, Yedizza, Stachon, Tanja, Szentmáry, Nóra, Lagali, Neil
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 02-11-2024 Nature Publishing Group Nature Portfolio
Subjects:	631/337 692/699/3161 Aniridia Cell differentiation Chromosome 5 Cornea Corneal inflammation Epithelial cells Extracellular signal-regulated kinase Eye diseases Humanities and Social Sciences Keratitis Lipopolysaccharides MiR-204-5p multidisciplinary PAX6 Pax6 protein Science Science (multidisciplinary) Stem cells MiR-204-5p PAX6 Keratitis Corneal inflammation Aniridia
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Summary:	Congenital aniridia is a rare eye disease characterized by loss of PAX6 protein leading to aniridia-associated keratopathy that significantly reduces vision. The miR-204-5p is a possible regulator of PAX6 function and here we evaluate its effect in multiple in vitro and in vivo models. In vitro, miR-204-5p overexpression suppressed vascular factor ANGPT1 in human limbal stem cells (T-LSC) and Pax6-knockdown LSC (mut-LSC), and in primary human limbal epithelial cells (LEC) at the gene and protein levels and following LPS stimulation. However, miR-204-5p inhibited VEGFA expression only in mut-LSCs and LPS-stimulated LEC. Also, miR-204-5p increased PAX6 expression in mut-LSC and differentiated corneal epithelial cells, but not in LEC. Topical miR-204-5p after LPS-induced keratitis in mice failed to suppress Vegfa , Angpt1 , Il-1β , and Tnf-α or rescue Pax6 levels in contrast to in vitro results, although it significantly reduced the inflammatory infiltrate in the cornea. In Pax6 Sey/+ aniridia mice, miR-204-5p did not rescue PAX6 levels or suppress Vegfa , Angpt1 , or inhibit the ERK1/2 pathway. While short-term miR-204-5p treatment effectively suppresses VEGFA and ANGPT1 and enhances PAX6 expression in multiple corneal epithelia, effects are variable across primary and immortalized cells. Effects of longer-term in vivo treatment, however, require further study.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-76654-w