Abstract
Purpose:
Optic neuritis is a demyelinating inflammation of the optic nerve that often occurs in multiple sclerosis (MS) patients. Loss of retinal ganglion cells (RGCs) and their axons also occurs in optic neuritis, and correlates with permanent vision loss. ACCS is a novel biologic mixture of growth factors and cytokines secreted from Amnion-derived Multipotent Progenitor (AMP) cells, that exhibits anti-inflammatory and neuroprotective properties in a variety of disease models. The ability of ACCS to suppress optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of MS was examined.
Methods:
EAE was induced in C57/BL6 mice by immunization with myelin oligodendroglial glycoprotein peptide. Mice were treated daily with one drop (6 uL) of ACCS intranasally beginning before or after onset of optic neuritis. Visual function was assessed by optokinetic responses (OKR) at baseline, then weekly until sacrifice 6 weeks post-immunization. Retinas and optic nerves were isolated. RGCs were immunolabeled with Brn3a antibodies to quantify RGC survival. Inflammation was assessed by H&E and Iba1 (macrophage/microglia marker) staining, demyelination by luxol fast blue staining, and axonal loss by neurofilament staining of optic nerve sections.
Results:
Progressive decreases in OKR occurred in vehicle-treated EAE mice, along with significant RGC loss, consistent with prior studies showing onset of optic neuritis occurring 12-15 days after EAE induction. Daily intranasal ACCS treatment beginning on day 0 (day of immunization), 15, 22, or 30, significantly reduced the level of vision loss, and treatment from day 0 or day 15 significantly attenuated RGC loss. ACCS also decreased the degree of demyelination and axonal loss, but had limited effects on the level of inflammation in the optic nerve.
Conclusions:
ACCS treatment attenuates RGC loss, preserves OKR responses, and reduces demyelination and axonal loss during experimental optic neuritis in EAE mice. ACCS exerts effects with treatment initiated before and after onset of optic neuritis, suggesting it may be useful as a preventative or abortive therapy. Results suggest ACCS is a potential treatment for optic neuritis that warrants further study. Furthermore, potent effects seen after intranasal administration suggest this may be a novel drug delivery method for optic neuritis.