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Reas Sulaimankutty, Kimberly Dine, Larry Brown, Kenneth S Shindler; Effects of Different Treatment Regimens in ST266-Mediated RGC Neuroprotection. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3351. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Optic neuritis is an optic nerve inflammation that occurs in multiple sclerosis (MS). Prior studies showed that intranasally administered ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells which contains multiple growth factors and anti-inflammatory cytokines, attenuated visual dysfunction and prevented retinal ganglion cell (RGC) loss in experimental optic neuritis, but long-term effects and effects of varying doses were not reported. Here, the ability of different ST266 treatment regimens to prevent neuronal damage during experimental optic neuritis was examined.
Optic neuritis was induced in the MS model experimental autoimmune encephalomyelitis (EAE) by immunization of 8 wk old C57/BL6 mice with myelin oligodendroglial glycoprotein peptide. Control mice were sham immunized with PBS. Mice were treated once or twice daily with 6 uL intranasal PBS, HSA or ST266 beginning day 15 post-immunization (after onset of optic neuritis) until day 30 or through sacrifice on day 56. Visual function was assessed by optokinetic responses (OKR) at baseline, then weekly. RGCs were immunolabeled with Brn3a antibodies in isolated retinas to quantify RGC survival.
Progressive decreases in OKR occurred in PBS and HSA treated EAE mice compared to control mice (p<0.001). Both once and twice daily ST266 treatment from day 15 to 56 significantly (p<0.05) increased OKR scores compared to PBS and HSA treated EAE mice, while ST266 dosing from day 15 to 30 did not improve OKR scores. Brn3a staining showed significant (p<0.001) RGC loss in PBS and HSA treated EAE mice compared to control mice. Once and twice daily ST266 treatment from day 15 to 56 each showed significant (p<0.001) RGC preservation compared to PBS and HSA treated EAE mice. Once daily ST266 from day 15 to 30 failed to prevent RGC loss, whereas twice daily ST266 from day 15 to 30 did increase RGC survival (p<0.05) compared to PBS or HSA treated EAE mice.
Both once and twice daily intranasal ST266 treatment show similar ability to preserve visual function and prevent RGC loss in EAE optic neuritis. With continued daily treatment, effects are maintained up to 8 weeks after EAE induction. Results confirm significant neuroprotection mediated by ST266 in optic neuritis, and suggest that once daily treatment may be sufficient to sustain maximal benefits of this novel therapy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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