Carboplatin induces optic nerve oligodendrocyte loss and impairs myelin sheath microstructure in a mouse model of neurofibromatosis type 1 (NF1)

While carboplatin-containing chemotherapy is often first-line therapy for NF1-OPG, it does not consistently improve visual function. Furthermore, chemotherapy is associated with altered white matter microstructure in individuals with NF1-OPG, suggesting a detrimental effect on oligodendroglia.

We analyzed the tumor-independent effects of carboplatin on oligodendrocytes in Nf1-mutant mice and evaluated pharmacological strategies for reducing this chemotherapy-associated toxicity. Carboplatin- or vehicle-treated Nf1+/- mice or Nf1-mutant optic glioma cells were employed to assess the effects of restorative interventions on optic nerve oligodendrocytes in vivo and tumor cell growth in vitro, respectively. Clinically relevant carboplatin dosing induced oligodendrocyte loss and impaired myelin sheath structure in the optic nerves of Nf1+/- mice, an effect not observed following MEK inhibitor (selumetinib) treatment.