Universität zu Köln

Feng, Yuan, Wang, Xiaosha ORCID: 0009-0003-8044-3951, Li, Panpan ORCID: 0000-0001-5777-0899, Shi, Xin ORCID: 0000-0002-6649-4045, Prokosch, Verena ORCID: 0000-0002-5318-0637 and Liu, Hanhan ORCID: 0000-0003-0204-1087 (2025). Exogenous hydrogen sulfide and NOX2 inhibition mitigate ferroptosis in pressure-induced retinal ganglion cell damage. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1871 (3). Elsevier. ISSN 0925-4439

PDF 1-s2.0-S092544392500050X-main.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution Non-commercial. Download (10MB)

Abstract

[Artikel-Nr. 167705] Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). While elevated intraocular pressure (IOP) significantly contributes to disease progression, managing IOP alone does not completely halt it. The mechanisms underlying RGCs loss in glaucoma remain unclear, but ferroptosis—an iron-dependent form of oxidative cell death—has been implicated, particularly in IOP-induced RGCs loss. There is an urgent need for neuroprotective treatments. Our previous research showed that hydrogen sulfide (H2S) protects RGCs against glaucomatous injury. This study aims to investigate the interplay between elevated pressure, mitochondrial dysfunction, iron homeostasis, and ferroptosis in RGCs death, focusing on how H2S may mitigate pressure-induced ferroptosis and protect RGCs. We demonstrate alterations in iron metabolism and mitochondrial function in a subacute IOP elevation model in vivo. In vitro, we confirm that elevated pressure, iron overload, and mitochondrial dysfunction lead to RGCs loss, increased retinal ferrous iron and total iron content, and heightened reactive oxygen species (ROS). Notably, pressure increases NADPH oxidase 2 (NOX2) and decreases glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis. NOX2 deletion or inhibition by H2S prevents pressure-induced RGCs loss and ferroptosis. Our findings reveal that H2S chelates iron, regulates iron metabolism, reduces oxidative stress, and mitigates ferroptosis, positioning slow-releasing H2S donors are positioning as a promising multi-target therapy for glaucoma, with NOX2 emerging as a key regulator of ferroptosis.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Feng, Yuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Xiaosha UNSPECIFIED https://orcid.org/0009-0003-8044-3951 UNSPECIFIED Li, Panpan UNSPECIFIED https://orcid.org/0000-0001-5777-0899 UNSPECIFIED Shi, Xin UNSPECIFIED https://orcid.org/0000-0002-6649-4045 UNSPECIFIED Prokosch, Verena UNSPECIFIED https://orcid.org/0000-0002-5318-0637 UNSPECIFIED Liu, Hanhan UNSPECIFIED https://orcid.org/0000-0003-0204-1087 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-797094
Identification Number:	10.1016/j.bbadis.2025.167705
Journal or Publication Title:	Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Volume:	1871
Number:	3
Number of Pages:	1
Date:	March 2025
Publisher:	Elsevier
ISSN:	0925-4439
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79709