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Reas Sulaimankutty; Preservation of retinal ganglion cell function and attenuation of axonal loss by HE3286, a synthetic derivative of natural steroid, Beta-AET during experimental optic neuritis. Journal of Vision 2014;14(15):81. doi: 10.1167/14.15.81.
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© ARVO (1962-2015); The Authors (2016-present)
Optic nerve inflammation, demyelination and axonal loss are all prominent features of optic neuritis. While corticosteroids can hasten visual recovery in optic neuritis, no treatment is available to improve visual outcomes. HE3286, a synthetic derivative of a natural steroid, β-AET exerts anti-inflammatory and has purported direct neuroprotective effects in several disease models. The ability of HE3286 to suppress optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis was examined. EAE was induced in C57/Bl6 mice by immunization with myelin oligodendroglial glycoprotein peptide. Mice were treated daily with vehicle or 40 mg/kg HE3286 i.p. Visual function was assessed by optokinetic responses (OKR) at every 10 days until sacrifice 6 weeks post-immunization. Retinas and optic nerves were isolated. Inflammation, demyelination and axonal loss in the optic nerve was assessed. Retinal ganglion cells (RGCs) were immunolabeled with Brn3a antibodies to quantify RGC survival. Progressive decreases in OKR occurred in vehicle-treated EAE mice, and HE3286 treatment significantly reduced the level of this vision loss. HE3286 also significantly attenuated the degree of inflammation, demyelination and axonal loss in EAE optic nerves as compared to nerves from vehicle-treated EAE mice. RGC loss was observed in eyes from both vehicle- and HE3286-treated EAE mice, with a trend toward increased RGC survival in the HE3286-treated mice. HE3286 suppresses inflammation and reduces demyelination and axonal loss during experimental optic neuritis. Importantly, HE3286 treatment also preserves some RGC function. Results suggest HE3286 is a potential novel treatment for optic neuritis and MS that warrants further study.
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