Contributions
Abstract: EP1634
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. The phase III ALLEGRO study demonstrated a reduction of lesion development, brain atrophy, relapse rate and progression of disability with(under?) laquinimod therapy. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties. However, its impact on the visual system, which is often affected by MS, is unknown.
Objective: To investigate a potential protective effect of laquinimod on optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model.
Methods: We immunized wild-type C57/BL6 mice with MOG35-55 to induce EAE. Five groups were investigated: an untreated EAE group, three EAE groups receiving laquinimod in doses of 1, 5, or 25 mg/kg daily, starting the day post-immunization, and a healthy control group without EAE. Neurological impairment was evaluated via scoring. 30 days post-immunization, scotopic electroretinograms were carried out and mice were sacrificed for histopathology, immunohistochemistry, and qRT-PCR. In the optic nerve, the extent of cellular infiltration (HE) and demyelination (LFB, MBP) was monitored. Microglia (Iba1) with macrophage function (F4/80) and macroglia (astrocytes, GFAP), including retinal Müller glia (vimentin), were examined in retina and optic nerve. Moreover, we investigated retinal ganglion cells (Brn-3a) and their rates of apoptosis (cleaved caspase-3).
Results: Laquinimod significantly reduced clinical EAE symptoms in a dose-dependent manner. In electroretinogram measurements, a protection of neurons in the inner nuclear layer could be noted. Laquinimod decreased signs of cellular infiltration (25 mg: p=0.002) and demyelination (25 mg: p< 0.001) in the optic nerve. Numbers of microglia, also with macrophage function, in optic nerves and retinas, were reduced. Retinal macroglial signal was diminished under treatment, whereas in the optic nerve more GFAP signal was found. Furthermore, laquinimod protected retinal ganglion cells (25 mg: p< 0.001) and lowered their apoptosis rate (25 mg: p< 0.029).
Conclusion: From our study, we deduce neuroprotective and anti-inflammatory effects of laquinimod on optic nerve and retina in EAE mice. Given the fact that the visual system is frequently affected by MS, the agent might be an interesting subject of further neuro-ophthalmic investigations.
Disclosure:
Stephanie C. Joachim: nothing to disclose
Anna T. Wilmes: nothing to disclose
Sandra Kühn. nothing to disclose
Xiomara Pedreiturria: nothing to disclose
Sabrina Reinehr: nothing to disclose
Ilya Ayzenberg: nothing to disclose
Gesa Stute: nothing to disclose
Ralf Gold: serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis
H. Burkhard Dick: nothing to disclose
Ingo Kleiter: received honoraria for consultancy or speaking and travel reimbursement from Bayer Healthcare, Chugai, Merck, Roche, and Shire, and grant support from Affectis, Biogen, Chugai and Diamed
Abstract: EP1634
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. The phase III ALLEGRO study demonstrated a reduction of lesion development, brain atrophy, relapse rate and progression of disability with(under?) laquinimod therapy. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties. However, its impact on the visual system, which is often affected by MS, is unknown.
Objective: To investigate a potential protective effect of laquinimod on optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model.
Methods: We immunized wild-type C57/BL6 mice with MOG35-55 to induce EAE. Five groups were investigated: an untreated EAE group, three EAE groups receiving laquinimod in doses of 1, 5, or 25 mg/kg daily, starting the day post-immunization, and a healthy control group without EAE. Neurological impairment was evaluated via scoring. 30 days post-immunization, scotopic electroretinograms were carried out and mice were sacrificed for histopathology, immunohistochemistry, and qRT-PCR. In the optic nerve, the extent of cellular infiltration (HE) and demyelination (LFB, MBP) was monitored. Microglia (Iba1) with macrophage function (F4/80) and macroglia (astrocytes, GFAP), including retinal Müller glia (vimentin), were examined in retina and optic nerve. Moreover, we investigated retinal ganglion cells (Brn-3a) and their rates of apoptosis (cleaved caspase-3).
Results: Laquinimod significantly reduced clinical EAE symptoms in a dose-dependent manner. In electroretinogram measurements, a protection of neurons in the inner nuclear layer could be noted. Laquinimod decreased signs of cellular infiltration (25 mg: p=0.002) and demyelination (25 mg: p< 0.001) in the optic nerve. Numbers of microglia, also with macrophage function, in optic nerves and retinas, were reduced. Retinal macroglial signal was diminished under treatment, whereas in the optic nerve more GFAP signal was found. Furthermore, laquinimod protected retinal ganglion cells (25 mg: p< 0.001) and lowered their apoptosis rate (25 mg: p< 0.029).
Conclusion: From our study, we deduce neuroprotective and anti-inflammatory effects of laquinimod on optic nerve and retina in EAE mice. Given the fact that the visual system is frequently affected by MS, the agent might be an interesting subject of further neuro-ophthalmic investigations.
Disclosure:
Stephanie C. Joachim: nothing to disclose
Anna T. Wilmes: nothing to disclose
Sandra Kühn. nothing to disclose
Xiomara Pedreiturria: nothing to disclose
Sabrina Reinehr: nothing to disclose
Ilya Ayzenberg: nothing to disclose
Gesa Stute: nothing to disclose
Ralf Gold: serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis
H. Burkhard Dick: nothing to disclose
Ingo Kleiter: received honoraria for consultancy or speaking and travel reimbursement from Bayer Healthcare, Chugai, Merck, Roche, and Shire, and grant support from Affectis, Biogen, Chugai and Diamed