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
- diabetic rats
- pi k akt
- nuclear factor
- poor prognosis
- cell therapy
- single cell
- estrogen receptor
- high glucose
- climate change
- inflammatory response
- young adults
- optical coherence tomography
- neuropathic pain
- magnetic resonance imaging
- drug induced
- adipose tissue
- binding protein
- optic nerve
- stem cells
- mesenchymal stem cells
- cell proliferation
- computed tomography
- spinal cord injury
- contrast enhanced
- bone marrow
- skeletal muscle
- case control