Optic nerve dysfunction in a mouse model of neurofibromatosis-1 optic glioma

Balazs Hegedus, Frank W. Hughes, Joel R. Garbow, Scott Gianino, Debasish Banerjee, Keunyoung Kim, Mark H. Ellisman, Milam A. Brantley, David H. Gutmann

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Individuals with neurofibromatosis type 1 (NF1) are prone to developoptic pathway gliomas that can result in significant visual impairment. To explore the cellular basis for the reduced visual functionresulting from optic glioma formation, we used a genetically engineered mouse model of Nf1 optic glioma (Nf1+/-CKO mice). We performed multimodal functional and structural analyses both before and after the appearance of macroscopic tumors. At 6weeks of age, before obvious glioma formation, Nf1+/-CKO mice had decreased visual-evoked potential amplitudes and increased optic nerve axon calibers. By 3 months of age, Nf1+/-CKO mice exhibited pronounced optic nerve axonopathy and apoptosis ofneurons in the retinal ganglion cell layer. Magnetic resonance diffusion tensor imaging showed a progressive increase in radial diffusivity between 6 weeks and 6 months of age in the optic nerve proximal to the tumor indicating ongoing deterioration of axons. These data suggest that optic glioma formation results in early axonaldisorganization and damage, which culminates in retinal ganglion cell death. Collectively, this study shows that Nf1+/-CKO mice can provide a useful model for defining mechanisms of visual abnormalities in children with NF1 and lay the foundations for future interventional studies aimed at reducing visual loss.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number5
DOIs
Publication statusPublished - May 1 2009

Keywords

  • Apoptosis
  • Magnetic resonance imaging
  • Neurofibromatosis-1
  • Optic pathway glioma
  • Retinal ganglion cell
  • Visualevoked potential

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Hegedus, B., Hughes, F. W., Garbow, J. R., Gianino, S., Banerjee, D., Kim, K., Ellisman, M. H., Brantley, M. A., & Gutmann, D. H. (2009). Optic nerve dysfunction in a mouse model of neurofibromatosis-1 optic glioma. Journal of Neuropathology and Experimental Neurology, 68(5), 542-551. https://doi.org/10.1097/NEN.0b013e3181a3240b