Estrogen-induced glial IL-1β mediates extrinsic retinal ganglion cell vulnerability in murine Nf1 optic glioma.
Yunshuo TangJit ChatterjeeNgan WagonerStephanie BozemanDavid H GutmannPublished in: Annals of clinical and translational neurology (2024)
Optic pathway gliomas (OPGs) arising in children with neurofibromatosis type 1 (NF1) can cause retinal ganglion cell (RGC) dysfunction and vision loss, which occurs more frequently in girls. While our previous studies demonstrated that estrogen was partly responsible for this sexually dimorphic visual impairment, herein we elucidate the underlying mechanism. In contrast to their male counterparts, female Nf1 OPG mice have increased expression of glial interleukin-1β (IL-1β), which is neurotoxic to RGCs in vitro. Importantly, both IL-1β neutralization and leuprolide-mediated estrogen suppression decrease IL-1β expression and ameliorate RGC dysfunction, providing preclinical proof-of-concept evidence supporting novel neuroprotective strategies for NF1-OPG-induced vision loss.
Keyphrases
- signaling pathway
- oxidative stress
- lps induced
- pi k akt
- diabetic rats
- poor prognosis
- nuclear factor
- cell therapy
- single cell
- high glucose
- estrogen receptor
- inflammatory response
- optical coherence tomography
- young adults
- magnetic resonance
- drug induced
- high grade
- type diabetes
- climate change
- binding protein
- stem cells
- long non coding rna
- bone marrow
- toll like receptor
- computed tomography
- cell proliferation
- spinal cord
- cerebral ischemia
- adipose tissue
- immune response
- rare case