Abstract
Purpose: :
Two thirds of eyes from mice with experimental autoimmune encephalomyelitis (EAE), a central nervous system demyelinating disease used as a model of multiple sclerosis, develop optic neuritis. Presence of optic neuritis is determined by histologic evaluation after mice are sacrificed, thus limiting the ability to monitor the progression or treatment of this experimental optic neuritis over time in vivo. We examined whether mouse pupillometry can be used to detect decreased optic nerve function in EAE mice with optic neuritis.
Methods: :
Wild-type C57Bl/6 mice were dark-adapted, then exposed to light flashes of increasing intensity at 10 second intervals (4.7, 37, and 300 µW/cm2). Pupillary responses were recorded with a Neuroptics Pupillometer (San Clemente, CA, USA). EAE was then induced by immunization with myelin oligodendroglial protein. Pupillometry was repeated in control and EAE mice every 1-2 days up to 17 days post-immunization. Following sacrifice, optic nerves were isolated and processed for histologic evaluation to detect presence of inflammatory cell infiltration.
Results: :
By day 14 post-immunization, almost half of the eyes of EAE mice developed histologic evidence of optic neuritis, with some eyes showing more than a 25% decrease in pupillary constriction compared to baseline and control mouse eyes. At day 17 post-immunization, almost all EAE eyes had detectable optic nerve inflammation. EAE eyes had significantly reduced pupillary constriction velocity and a reduced area of pupillary constriction as compared to control mouse eyes.
Conclusions: :
Results suggest that pupillometry can be useful for detecting decreased optic nerve function in mice with experimental optic neuritis. Detection of reduced pupillary constriction will allow identification of eyes with optic neuritis in vivo, and allow functional assessment of potential therapies for optic neuritis over time in mouse disease models.
Keywords: optic nerve • pupil • inflammation