Journal article
Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis
Frontiers in immunology, Vol.14, 1271118
10/23/2023
DOI: 10.3389/fimmu.2023.1271118
PMCID: PMC10628762
PMID: 37942317
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. 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. 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. 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.
Details
- Title: Subtitle
- Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis
- Creators
- Jeffrey J. AndersBenjamin W. ElwoodRandy H. KardonOliver W. Gramlich
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.14, 1271118
- DOI
- 10.3389/fimmu.2023.1271118
- PMID
- 37942317
- PMCID
- PMC10628762
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Language
- English
- Date published
- 10/23/2023
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984503056702771
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