Purchase this article with an account.
Oliver W Gramlich, Kasra Zarei, Alexander J Brown, Randy H Kardon; Early Visual Biomarkers in a Mouse Model of Multiple Sclerosis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):620. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Optic neuritis is an associated pathology of Multiple Sclerosis (MS), and is often the first symptom of the disease. The purpose of our study is to determine if functional and structural assessments of the visual system could provide early biomarkers to predict MS relapses in an experimental autoimmune encephalomyelitis (EAE) model.
EAE was induced in 12 female C57BL6 mice by immunization with MOG33-55, complete Freunds adjuvant and pertussis toxin. 12 sham-injected (sham) served as controls. Clinical progression was recorded according to a 5-point EAE scoring scheme. Pattern electroretinography (PERG) was recorded at baseline, 4, 11, 18, 25, and 32 days after induction. Retinal thickness was determined by optical coherence tomography prior to death at day 35 and retinal ganglion cell (RGC) density was examined via Brn3a immunostaining afterwards.
Motor-sensory deficits were apparent 10 days after induction. Significant delayed PERG conduction speed in EAE mice was evident as early as 4 days after induction (sham: 170±29ms vs. EAE: 210±45ms; P=0.03) and latency remained prolonged at later time points (P<0.05). EAE mice also demonstrate a significant decrease in the PERG amplitude at day 25 (ctrl: 28±6µV vs. EAE: 21±6µV; P=0.02) and at day 32 (sham: 28±2µV vs. EAE: 24±5µV; P=0.02). PERG amplitude and retinal thickness in EAE mice moderately correlated (R=0.59). EAE mice displayed a pronounced loss of RGC in the mid-peripheral retina when compared to sham-immunized mice (sham: 3602±290 RGC/mm2 vs. EAE: 3130±251 RGC/mm2; P=0.03).
Herein we describe that decreased optic nerve conduction velocity precedes motor-sensory and structural deficits in the EAE model. Our data also suggest that the impairment of visual function corresponds to retinal thinning and RGC loss. Clinical translation of these results could help predict MS relapses and rehabilitation in MS patients.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only