June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Targeting Cholesterol Homeostasis Improves Recovery In Experimental Optic Neuritis
Author Affiliations & Notes
  • Cheyanne Godwin
    Ophthalmology, University of Iowa, Iowa City, Iowa, United States
  • Lin Cheng
    Center for the Prevention and Treatment of Visual Loss, Iowa City VA Medical Center, Iowa City, Iowa, United States
  • Jeffrey Anders
    Ophthalmology, University of Iowa, Iowa City, Iowa, United States
    Center for the Prevention and Treatment of Visual Loss, Iowa City VA Medical Center, Iowa City, Iowa, United States
  • Benjamin Elwood
    Ophthalmology, University of Iowa, Iowa City, Iowa, United States
    Center for the Prevention and Treatment of Visual Loss, Iowa City VA Medical Center, Iowa City, Iowa, United States
  • Randy H Kardon
    Ophthalmology, University of Iowa, Iowa City, Iowa, United States
    Center for the Prevention and Treatment of Visual Loss, Iowa City VA Medical Center, Iowa City, Iowa, United States
  • Oliver W Gramlich
    Ophthalmology, University of Iowa, Iowa City, Iowa, United States
    Center for the Prevention and Treatment of Visual Loss, Iowa City VA Medical Center, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Cheyanne Godwin None; Lin Cheng None; Jeffrey Anders None; Benjamin Elwood None; Randy Kardon None; Oliver Gramlich None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 430. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Cheyanne Godwin, Lin Cheng, Jeffrey Anders, Benjamin Elwood, Randy H Kardon, Oliver W Gramlich; Targeting Cholesterol Homeostasis Improves Recovery In Experimental Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):430.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Magnitude of cholesterol rich myelin debris clearance after demyelination in Multiple Sclerosis (MS) limits recovery. The purpose of our study is to determine if augmentation of cholesterol efflux transporter 1 (Abca1) by gentisic acid (GA) influences synaptogenesis, myelination, and rescue of the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) optic neuritis model.

Methods : Brain organoids and Brn3a-GFP expressing retinal organoids were grown with or without 400µM GA. Organoids were analyzed for Abca1, PSD95, NG2, and Olig2 expression. EAE-related optic neuritis was induced in 52 female C57BL6 mice by immunization with MOG33-55, complete Freund’s Adjuvant and pertussis toxin. 22 EAE mice received intraperitoneal GA weekly (EAE+GA), another 25 naïve mice served as controls. Clinical progression was monitored using a 5-point EAE scoring scheme. At day 60, visual acuity, pattern electroretinography (PERG) and retinal ganglion cell (RGC) complex thickness were measured. Grades of demyelination and cell infiltration in optic nerves were determined. Differences were evaluated using Tukey’s post-hoc test.

Results : Retinal organoids+GA show accelerated maturation, evident by increased number of Brn3a+RGC and increased expression of PSD95. Brain organoids+GA demonstrated a 10-fold increase in NG2 and Olig2 expression as well as a 4-fold increase in PLP. EAE+GA animals show significantly lower motor-sensory impairment (EAE:122±4 vs. EAE+GA: 78±5; p=0.0001). Treatment also preserved visual acuity (EAE:0.23±0.08c/d vs. EAE+GA: 0.34±0.09c/d; p=0.0001), improved the PERG amplitude (EAE:16±4 vs. EAE+GA:20±4 µV; p=0.03) and slightly diminished RGC complex thinning (EAE:59±4µm vs. EAE+GA:62±3µm; p=0.2) when compared to untreated EAE mice. Grades of demyelination in the optic nerve was less severe in EAE+GA mice (EAE:2.1±0.8 vs. EAE+GA: 1.1±0.6; p=0.0001) and fewer infiltrating cells were observed (EAE:2.2±1 vs. EAE+GA: 1±0.5; p=0.0001).

Conclusions : GA supplementation in organ specific organoids accelerates retinal development and myelination. In EAE mice, GA administration significantly lessens motor-sensory deficits and promotes visual system recovery that is related to increased clearing of myelin debris and preservation of synaptic plasticity. In summary, this study suggests that interventions to improve cholesterol homeostasis might be a viable approach to promote rehabilitation in MS.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×