THE ROLE OF MICROGLIAL CELLS IN NEUROINFLAMMATORY CONDITIONS

Multiple sclerosis is a chronic inflammatory and neurodegenerative disorder. Microglial cells contribute to both tissue damage and homeostasis, but their context-dependent roles in multiple sclerosis remain incompletely defined. This study assessed pharmacological microglia cell depletion on disease trajectory and visual pathway integrity in an experimental autoimmune encephalomyelitis–optic neuritis (EAE-ON) model. EAE-ON was induced in CX3CR1-GFP transgenic mice by MOG 35–55 immunization. Microglial cells were depleted using CSF1R inhibitor Pexidartinib (PLX3397) from day 3 to 16 post-immunization. A separate cohort was examined after withdrawal of treatment to investigate the repopulation of microglial cells in the chronic phase of EAE on day 35. In vivo retinal changes were quantified by optical coherence tomography (OCT) and the GFP-positive microglial cells were tracked longitudinally via confocal scanning laser ophthalmoscopy. The visual function was assessed by optomotor response (OMR). Immune profiles in spleen and spinal cord were analyzed by flow cytometry, supported by histopathological analysis. Microglial cell depletion markedly reduced EAE severity at peak disease, with lower clinical scores and improved OMR performance. However, OCT revealed a trend toward greater retinal neurodegeneration despite better vision potential. In the chronic phase, clinical disability equalized between depleted and control groups. PLX treatment reduced dendritic cells, including conventional DCs, in the spleen at peak disease. Spinal cord immune composition showed minimal changes. These data highlight the dual role of microglial cells, which can exert both neuroprotective and neurodegenerative functions in neuroinflammatory diseases like multiple sclerosis.