Targeting Cholesterol Homeostasis Improves Recovery in Experimental Optic Neuritis

Cheyanne R. Godwin; Jeffrey J. Anders; Lin Cheng; Benjamin W. Elwood; Randy H. Kardon; Oliver W. Gramlich

doi:10.3390/biom12101437

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Targeting Cholesterol Homeostasis Improves Recovery in Experimental Optic Neuritis

Journal article

Open access

Peer reviewed

Targeting Cholesterol Homeostasis Improves Recovery in Experimental Optic Neuritis

Cheyanne R. Godwin, Jeffrey J. Anders, Lin Cheng, Benjamin W. Elwood, Randy H. Kardon and Oliver W. Gramlich

Biomolecules (Basel, Switzerland), Vol.12(10), p.1437

10/07/2022

DOI: 10.3390/biom12101437

PMCID: PMC9599133

PMID: 36291646

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Abstract

Acute optic neuritis (ON) is a common cause of vision loss and is often associated with multiple sclerosis (MS). Cholesterol recycling has been identified as a key limiting factor in recovery after demyelination events. Thus, the purpose of our study was to determine if the augmentation of cholesterol transport by gentisic acid (GA) benefits retinal ganglion cell (RGC) development and myelination in organoid systems and enables the recovery of the ocular phenotype upon systemic GA treatment in a MOG-induced experimental autoimmune encephalomyelitis (EAE) ON model. The retinal organoids treated with GA demonstrate an accelerated maturation when compared to the conventionally derived organoids, which was evidenced by the improved organization of Brn3a-GFP + RGC and increased synaptogenesis. A GA supplementation in brain organoids leads to a 10-fold increase in NG2 and Olig2 expression. Weekly GA injections of EAE mice significantly lessened motor-sensory impairment, protected amplitudes in pattern electroretinogram recordings, and preserved visual acuity over the study period of 56 days. Furthermore, GA-treated EAE mice revealed diminished GCL/IPL complex thinning when compared to the untreated EAE mice. An optic nerve histopathology revealed less severe grades of demyelination in the GA-treated EAE cohort and fewer infiltrating cells were observed. Interventions to improve cholesterol homeostasis may be a viable approach to promoting the rehabilitation of MS patients.

Electrophysiology

Multiple Sclerosis

cholesterol recycling

EAE

gentisic acid

optic neuritis

organoids

RGC

Details

Title: Subtitle: Targeting Cholesterol Homeostasis Improves Recovery in Experimental Optic Neuritis
Creators: Cheyanne R. Godwin - Iowa City VA Health Care System
Jeffrey J. Anders - University of Iowa
Lin Cheng - University of Iowa
Benjamin W. Elwood - University of Iowa
Randy H. Kardon - University of Iowa
Oliver W. Gramlich - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, Iowa City, IA 52246, USA Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Biomolecules (Basel, Switzerland), Vol.12(10), p.1437
DOI: 10.3390/biom12101437
PMID: 36291646
PMCID: PMC9599133
NLM abbreviation: Biomolecules
eISSN: 2218-273X
Publisher: MDPI
Grant note: 1I50RX003002-01 / United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service
Language: English
Date published: 10/07/2022
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9984307660002771

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