Characterization of Retinal Ganglion Cell and Optic Nerve Phenotypes Caused by Sustained Intracranial Pressure Elevation in Mice

Guofu Shen, Schuyler Link, Sandeep Kumar, Derek M. Nusbaum, Yan Yin Tse, Yingbin Fu, Samuel M. Wu, Benjamin J. Frankfort

Research output: Journal article publicationJournal articleAcademic researchpeer-review

8 Citations (Scopus)


Elevated intracranial pressure (ICP) can result in multiple neurologic sequelae including vision loss. Inducible models of ICP elevation are lacking in model organisms, which limits our understanding of the mechanism by which increased ICP impacts the visual system. We adapted a mouse model for the sustained elevation of ICP and tested the hypothesis that elevated ICP impacts the optic nerve and retinal ganglion cells (RGCs). ICP was elevated and maintained for 2 weeks, and resulted in multiple anatomic changes that are consistent with human disease including papilledema, loss of physiologic cupping, and engorgement of the optic nerve head. Elevated ICP caused a loss of RGC somas in the retina and RGC axons within the optic nerve, as well as a reduction in both RGC electrical function and contrast sensitivity. Elevated ICP also caused increased hypoxia-inducible factor (HIF)-1 alpha expression in the ganglion cell layer. These experiments confirm that sustained ICP elevation can be achieved in mice and causes phenotypes that preferentially impact RGCs and are similar to those seen in human disease. With this model, it is possible to model human diseases of elevated ICP such as Idiopathic Intracranial Hypertension and Spaceflight Associated Neuro-ocular Syndrome.
Original languageEnglish
Article number2856
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2018

ASJC Scopus subject areas

  • General

Cite this