title: In vivo detection of experimental optic neuritis by pupillometry.
abstract: Optic neuritis is an inflammatory demyelination of optic nerve often occurring in multiple sclerosis (MS) patients. Mice with experimental autoimmune encephalomyelitis (EAE), an MS model, develop optic neuritis, but it is detected histologically after sacrifice, limiting the ability to monitor progression or treatment in vivo. We examined whether pupillary light responses measured by pupillometry can identify eyes with optic neuritis in EAE mice. C57BL/6 mice were exposed to unilateral light flashes of increasing intensity at 10 s intervals (4.7, 37, and 300 μW/cm(2)). Pupillary responses were recorded with a commercially available pupillometer. EAE was then induced by immunization with myelin oligodendrocyte glycoprotein. Pupillometry was repeated up to 17 days post-immunization, and responses were correlated with optic nerve inflammation. By day 17 post-immunization, 90% of EAE eyes had optic nerve inflammation. EAE eyes had significantly reduced pupillary constriction compared to control eyes. Mice exhibited more than a 25% decrease in pupillary constriction in at least one eye by days 13-15 post-immunization. In some eyes, pupil responses decreased prior to onset of detectable inflammation. Results show that pupillometry detects decreased optic nerve function in experimental optic neuritis, even in the absence of histological detection. Measuring pupillary constriction allows in vivo identification and functional assessment of eyes with optic neuritis that will be useful in evaluating potential therapies over time. Furthermore, results demonstrate that decreased visual function occurs early in optic neuritis, before optic nerve inflammation reaches its peak level.
authors.affiliation: F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Stellar-Chance Laboratories, 3rd Floor, 422 Curie Blvd, Philadelphia, PA 19104, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Shindler
authors.forename: Karen
authors.initials: K
authors.lastname: Revere
authors.forename: Mahasweta
authors.initials: M
authors.lastname: Dutt
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chung
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis*; D005260:Female; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009900:Optic Nerve / Q000473:pathology*; D009902:Optic Neuritis / Q000175:diagnosis*; D011680:Pupil / Q000528:radiation effects*; D012025:Reflex, Pupillary
chemical_list: C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein