Investigate and Target an Inflammatory Response During NF1-OPG Formation
Abstract
While most NF1 patients with optic pathway gliomas (NF1-OPGs) have excellent survival, approximately 30% will experience vision loss despite treatment.Recent imaging studies have shown that loss of retinal ganglion cells (RGCs) the only neuronal population connecting the eye to the brain is associated with vision loss in NF1-OPG patients. However, the mechanism(s) underlying OPG-associated loss of RGCs and vision remains largely unknown. Using a newly developed NF1-OPG model, we found that Nf1-deficient (Nf1-/-) migrating glial progenitors (GPs) abnormally maintained stem/progenitor-like characteristics and were associated with an inflammatory response of increased numbers of Iba1+ microglia, and subsequent axonal/myelin degeneration and Bax-mediated apoptosis of RGCs. Accordingly, we hypothesize that abnormally differentiated Nf1-/- migrating GPs induces abnormal infiltration of microglia, triggering axonal/myelin degeneration and RGC death. To test this hypothesis, we propose three specific aims. Aim 1: To determine the source(s)and phenotypic abnormalities of increased infiltrating Iba1+ microglia by Nf1-/- migrating GPs. Aim 2: To transiently eliminate or immuno metabolically modulate microglia as a means to prevent or alleviate OPG-associated nerve injury and RGC death. Aim 3: To determine the mechanism inducing abnormal microglial infiltration by using the Mosaic Analysis with Double Markers (MADM) model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1227033
Entities
People
- Han-yu Shih
Organizations
- National Eye Institute