“…Second, specifically in female mice, gonadal estradiol acts through the estrogen receptor β (ERβ) to stimulate Nf1‐ mutant microglia, thereby causing Nf1 ‐mutant RGC death, thinning of the RNFL (which comprises RGC axons), and decreased visual acuity (Diggs‐Andrews, Brown, Gianino, Rubin, et al, ; Toonen, Solga, Ma, & Gutmann, ). Sexually dimorphic retinal pathology in Nf1 optic glioma mice is independent of tumor size and can be corrected by pharmacologic inhibition of microglial activation, ERβ blockade, or chemical or surgical ovariectomy (Toonen, Solga, et al, ). In this cell nonautonomous mechanism, microglia are hypothesized to secrete neurotoxic cytokines (e.g., IL‐1β) that either directly or indirectly damage RGC axons (Figure d), perhaps through disruption of normal axo‐glial contacts as seen in other forms of axonal injury (Howell et al, ).…”