Antibody mediated retinal damage in a NMO animal model

Abstract

Purpose : Neuromyelitis optica (NMO) is an autoimmune-inflammatory CNS disease mostly affecting the optic nerve and spinal cord. The impact on the visual pathway, especially loss of vision, can be severe for the patients. However, the pathogenic effects of autoantibodies directed against myelin oligodendrocyte glycoprotein (MOG) is not well understood yet. Therefore, we investigated the impact of those autoantibodies to the visual system to get a better understanding of the mechanisms of degeneration.

Methods : We used opticospinal encephalomyelitis (OSE) mice which are double-transgenic (2D2/Th) animals with a C57Bl/6 background that develop EAE spontaneously. The clinical score of the disease was evaluated daily on a scale from 0 to 10. At six weeks of age, the retinal morphology and its function was evaluated by optical coherence tomography (OCT) as well as electroretinography (ERG). Additionally, retinal layers were measured on H&E stained cross-sections. Retinal ganglion cells were analyzed via immunohistochemistry (RBPMS). Statistics were performed using student’s t-test.

Results : OSE mice showed clinical symptoms of encephalomyelitis with flaccid hind limb paralysis. A significantly higher score was observed in six week old OSE mice (p<0.0001), while control mice remained healthy. A-wave amplitudes were significantly reduced at 10 and 25 cd.s/m² flash intensity in the OSE compared to the control group after 6 weeks (p<0.05). A decreasing trend of the b-wave amplitude could be seen at flash intensities of 0.1 and 0.3 cd.s/m² in OSE animals in comparison to the control group. A significant reduction could be noticed at flash intensities of 1 up to 25 cd.s/m² in the OSE mice (p<0.05). Significantly fewer RBPMS⁺ cells were noted in OSE mice (47.5±4.0 cells/mm) compared to controls (68.3±9.2 cells/mm; p=0.042).

Conclusions : Our data show that not only clinical neurological symptoms, but also retinal damage occurs in animals with autoreactive T-cells to MOG. Loss of retinal functionality as well as fewer retinal ganglion cells were detected at a very early stage. Therefore, not only the spinal cord and the optic nerve seem to be affected by autoantibodies but also the retina.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.