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Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.
- Source :
-
Frontiers in immunology [Front Immunol] 2023 Oct 23; Vol. 14, pp. 1271118. Date of Electronic Publication: 2023 Oct 23 (Print Publication: 2023). - Publication Year :
- 2023
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Abstract
- Introduction: Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model.<br />Methods: EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg. Changes in the visual function and structure of ACF-treated EAE mice were compared to those of placebo-injected EAE mice and naïve control mice.<br />Results: ACF treatment improved motor-sensory impairment along with preserving visual acuity and optic nerve function. Analysis of retinal ganglion cell complex alsoshowed preserved thickness correlating with increased survival of retinal ganglion cells and their axons. Optic nerve cell infiltration and magnitude of demyelination were decreased in ACF-treated EAE mice. Subsequent in vitro studies revealed improvements not only attributed to the inhibition of HIF-1 butalso to previously unappreciated interaction with the eIF2a/ATF4 axis in the unfolded protein response pathway.<br />Discussion: This study suggests that ACF treatment is effective in an animal model of MS via its pleiotropic effects on the inhibition of HIF-1 and UPR signaling, and it may be a viable approach to promote rehabilitation in MS.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2023 Anders, Elwood, Kardon and Gramlich.)
- Subjects :
- Female
Animals
Mice
Acriflavine pharmacology
Acriflavine therapeutic use
Acriflavine metabolism
Mice, Inbred C57BL
Retinal Ganglion Cells metabolism
Encephalomyelitis, Autoimmune, Experimental drug therapy
Encephalomyelitis, Autoimmune, Experimental metabolism
Optic Neuritis drug therapy
Multiple Sclerosis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 37942317
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1271118