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K.S. Shindler, P. Tabuena, E. Ventura, A.M. Rostami; Corticosteroids Suppress Inflammation and Prevent Retinal Ganglion Cell Loss During Acute Optic Neuritis in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4840.
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© ARVO (1962-2015); The Authors (2016-present)
Mice with experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, develop optic neuritis, determined histologically by inflammatory cell infiltration of the optic nerve, beginning 9 days after immunization to induce EAE. Significant retinal ganglion cell (RGC) loss occurs in eyes with optic neuritis, however this is not detected until 14 days after immunization, raising the question whether RGC loss is a primary process or occurs secondary to inflammation. The current study examined whether RGC death during optic neuritis is induced by inflammation.
RGCs were retrogradely labeled with the fluorescent marker Fluorogold by stereotactic injections into the superior colliculi. EAE was induced one week later by immunization of SJL/J mice with proteolipid protein peptide 139–151. Mice were treated daily beginning on the day of immunization with subcutaneous injections of 200 µg/kg dexamethasone or PBS for 14 days. Mice were observed daily for clinical signs of EAE and scored on a 5 point scale. Mice were sacrificed on day 14 and RGC numbers were counted by fluorescent microscopy of dissected retinas. Optic neuritis was detected by inflammatory cell infiltration of longitudinal sections of fixed optic nerves stained with hematoxylin and eosin.
Dexamethasone treatment completely blocked clinical EAE, whereas PBS treated immunized mice developed typical neurological deficits with an average EAE score of 1.5 by day 14. Over 60% of eyes from EAE mice treated with PBS developed inflammatory cell infiltration of the optic nerve, similar to previous studies, whereas less than 5% of eyes from dexamethasone treated mice developed optic neuritis. EAE eyes with optic neuritis had significant loss of RGCs (> 30%) as compared to control eyes. Dexamethasone treatment prevented this RGC loss, with RGC numbers equivalent to control eyes.
The corticosteroid dexamethasone suppresses the inflammatory cell infiltration of the optic nerve that occurs during acute optic neuritis in EAE mice and prevents loss of RGCs. These results suggest that RGC loss is induced by the inflammatory process in optic neuritis. Anti–inflammatory therapy during optic neuritis is likely to have neuroprotective effects for RGCs.
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