Contributions
Abstract: P1085
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - OCT
Background: Neurodegeneration is a major cuase of disability in Multiple Sclerosis (MS). This degeneration is not accessible to conventional immunosuppressant and most immunomodulatory therapy. Fingolimod (FTY720) is used as immunomodulatory treatment of MS. It has been reported to reduce cerebral volume loss in MS patients, to diminish the size of infarctions in animal models of ischemic stroke and to protect from light induced retinal degeneration in rats suggesting possible neuroprotective effects.
Objective: We aimed to analyze the protective capacities of FTY720 on retinal degeneration in myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, as animal model of MS and optic neuritis and after optic nerve crush (also C57BL/6) as a model for non-inflammatory axonal injury.
Design/Methods: To assess retinal neurodegeneration we used latest generation spectral domain optical coherence tomography (OCT), histological staining of retinal ganglion cells in retinal wholemounts as well as histological evaluation of microglial activation, lymphocytic infiltration and demyelination in optic nerves.
Results: A prophylactic FTY720 treatment improved the clinical EAE score and prevented from the degeneration of the inner retinal layers, consisting of the retinal nerve fiber layer, ganglion cell layer and inner plexiform layer. Staining of the ganglion cells in retinal wholemounts and histology of the optic nerves in EAE revealed similar protective effects of FTY720 on ganglion cells and less lymphocytic infiltrates, less microglial activation and less demyelination in optic nerves, respectively.
In the optic nerve crush model, the beneficial effects could not be confirmed by OCT or histology.
Conclusion: This research is of high relevance as it evaluates the effects of FTY720 on neurodegeneration in vivo under well controlled experimental conditions using state of the art optical coherence tomography (OCT) technology. Our data provide further evidence that FTY720 treatment can prevent neuro-axonal loss in the context of autoimmune diseases of the central nervous system. At the same time, our results suggest that FTY720 may not be the ideal substance to prevent non-inflammatory neuroaxonal degeneration.
Disclosure: Michael Dietrich: nothing to disclose, Niklas Helling : nothing to disclose, Andrea Issberner: nothing to disclose, Alexander Hilla: nothing to disclose, Annemarie Heskamp: nothing to disclose, Carsten Berndt: nothing to disclose, Dietmar Fischer: nothing to disclose
Hans-Peter Hartung received grants from the Walter and Ilse Rose Stiftung, the Eugène Devic European Network (EU-FP7) and the German Ministry for Education and Research, received honoraria for consultancy from Bayer Health Care, Biogen Idec, Genzyme, Novartis, Teva, Sanofi Aventis, Hoffman La Roche and holds patents.
Orhan Aktas received grants from the German Research Foundation (DFG), Eugène Devic European Network (EU-FP7), German Ministry for Education and Research, Schaufler Foundation, honoraria for lectures from Novartis, Bayer Schering, Teva, Biogen Idec, holds patents and received travel/accommodations/meeting expenses from Novartis, Bayer Schering, and Merck Serono.
Philipp Albrecht received research grants from Novartis, Biogen Idec, Teva, Merz Pharmaceuticals and travel/accommodations/meeting expenses by Novartis, Teva, Biogen Idec, Merz Pharmaceuticals, Ipsen, Esai and Glaxo Smith Kline.
Abstract: P1085
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - OCT
Background: Neurodegeneration is a major cuase of disability in Multiple Sclerosis (MS). This degeneration is not accessible to conventional immunosuppressant and most immunomodulatory therapy. Fingolimod (FTY720) is used as immunomodulatory treatment of MS. It has been reported to reduce cerebral volume loss in MS patients, to diminish the size of infarctions in animal models of ischemic stroke and to protect from light induced retinal degeneration in rats suggesting possible neuroprotective effects.
Objective: We aimed to analyze the protective capacities of FTY720 on retinal degeneration in myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, as animal model of MS and optic neuritis and after optic nerve crush (also C57BL/6) as a model for non-inflammatory axonal injury.
Design/Methods: To assess retinal neurodegeneration we used latest generation spectral domain optical coherence tomography (OCT), histological staining of retinal ganglion cells in retinal wholemounts as well as histological evaluation of microglial activation, lymphocytic infiltration and demyelination in optic nerves.
Results: A prophylactic FTY720 treatment improved the clinical EAE score and prevented from the degeneration of the inner retinal layers, consisting of the retinal nerve fiber layer, ganglion cell layer and inner plexiform layer. Staining of the ganglion cells in retinal wholemounts and histology of the optic nerves in EAE revealed similar protective effects of FTY720 on ganglion cells and less lymphocytic infiltrates, less microglial activation and less demyelination in optic nerves, respectively.
In the optic nerve crush model, the beneficial effects could not be confirmed by OCT or histology.
Conclusion: This research is of high relevance as it evaluates the effects of FTY720 on neurodegeneration in vivo under well controlled experimental conditions using state of the art optical coherence tomography (OCT) technology. Our data provide further evidence that FTY720 treatment can prevent neuro-axonal loss in the context of autoimmune diseases of the central nervous system. At the same time, our results suggest that FTY720 may not be the ideal substance to prevent non-inflammatory neuroaxonal degeneration.
Disclosure: Michael Dietrich: nothing to disclose, Niklas Helling : nothing to disclose, Andrea Issberner: nothing to disclose, Alexander Hilla: nothing to disclose, Annemarie Heskamp: nothing to disclose, Carsten Berndt: nothing to disclose, Dietmar Fischer: nothing to disclose
Hans-Peter Hartung received grants from the Walter and Ilse Rose Stiftung, the Eugène Devic European Network (EU-FP7) and the German Ministry for Education and Research, received honoraria for consultancy from Bayer Health Care, Biogen Idec, Genzyme, Novartis, Teva, Sanofi Aventis, Hoffman La Roche and holds patents.
Orhan Aktas received grants from the German Research Foundation (DFG), Eugène Devic European Network (EU-FP7), German Ministry for Education and Research, Schaufler Foundation, honoraria for lectures from Novartis, Bayer Schering, Teva, Biogen Idec, holds patents and received travel/accommodations/meeting expenses from Novartis, Bayer Schering, and Merck Serono.
Philipp Albrecht received research grants from Novartis, Biogen Idec, Teva, Merz Pharmaceuticals and travel/accommodations/meeting expenses by Novartis, Teva, Biogen Idec, Merz Pharmaceuticals, Ipsen, Esai and Glaxo Smith Kline.