Evaluation of neuroprotective properties of dimethylfumarate by optical coherence tomography in non-inflammatory models of retinal neurodegeneration (P2.163)

Objective: To investigate if DMF has neuroprotective effects independent of immunomodulation we evaluated its effects in the non-inflammatory animal models of light-induced photoreceptor loss and optic nerve crush. Retinal neurodegeneration was assessed longitudinally by in-vivo retinal imaging using optical coherence tomography (OCT), and by glutathione (GSH) measurement and histological staining. Background: While great advances have been made in the immunomodulatory treatment of Multiple Sclerosis (MS) there is still an unmet need for drugs with neuroprotective potential. Dimethyl fumarate (DMF) has been suggested to exert both immunomodulatory and neuroprotective effects in MS. Design/Methods For light-induced photoreceptor loss, one eye of C57BL/6J mice was irradiated with an LED cold light lamp while for optic nerve crush the optic nerve was clamped behind the eye bulb. The other eye served as control. Retinal neurodegeneration was assessed by spectral domain OCT. GSH was measured in the choroid and retina and histological stainings of the retina (Iba1) were performed. Mice were treated with 30 mg DMF/kg bodyweight or vehicle. Results: While no protective effects were observed in optic nerve crush, in the light-induced retinal degeneration model, DMF treatment significantly reduced retinal degeneration. In these mice, the GSH levels in the retina and surrounding choroid were increased and histologically we detected less microglial activation in the outer retinal layers. Conclusions: DMF has no effects on traumatic axonal damage but provided significant neuroprotection during light-induced retinal overstimulation. This protection involves increased GSH tissue levels and a reduction of microglial activation suggesting both antioxidant and anti-inflammatory effects. Study Supported by: The research was supported by grants of the charitable Dr. Robert Pfleger Stiftung and Biogen to Philipp Albrecht Disclosure: Dr. Dietrich has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Issberner has nothing to disclose. Dr. Hecker has nothing to disclose. Dr. Kohne has nothing to disclose. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, GeNeuro, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Octapharma, Opexa Therapeutics, Teva Pharmaceuticals, MedImmune, Bayer HealthCare, Forward Pharma, and Roche. Dr. Albrecht has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Merck, Bayer-Healthcare, Allergan, Biogen, IPSEN, Merz, Novartis, TEVA. Dr. Albrecht has received research support from Biogen, Ipsen, Novartis and Roche.