title: Timing of corticosteroid therapy is critical to prevent retinal ganglion cell loss in experimental optic neuritis.
abstract: OBJECTIVE
  Acute vision loss from optic neuritis typically resolves; however, recovery is often not complete. Permanent vision loss from retinal ganglion cell (RGC) death occurs in 40% to 60% of patients. Current therapy (high-dose corticosteroids) speeds recovery but does not change final visual outcomes. Here the authors examined whether corticosteroids administered early in the disease course can prevent RGC loss in experimental optic neuritis.
  
  
  METHODS
  RGCs were retrogradely labeled with fluorogold in SJL/J mice. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with proteolipid protein peptide. Optic neuritis began 9 days after immunization. Mice were treated daily with dexamethasone, methylprednisolone, or PBS from days 0 to 14 or days 10 to 14 and then were killed on day 14, 18, or 22.
  
  
  RESULTS
  Corticosteroid treatment initiated before optic neuritis onset (days 0-14) suppressed EAE and reduced optic neuritis incidence through day 14. In the few eyes that developed optic neuritis, inflammation was mild, and RGC loss was attenuated. After treatment was stopped on day 14, mice rapidly developed EAE and optic neuritis by day 18, but RGC loss was still reduced. By day 22, RGC loss increased to levels similar to those of untreated optic neuritis eyes. Corticosteroid treatment after optic neuritis onset (days 10-14) slowed EAE progression and showed a trend toward suppression of optic neuritis and RGC loss on day 14 that was lost by day 18.
  
  
  CONCLUSIONS
  Corticosteroids can suppress optic neuritis and prevent RGC loss if treatment is initiated before optic nerve inflammation onset. Treatment is less effective after inflammation begins. Results suggest that chronic immunomodulation may prevent recurrent optic neuritis and RGC damage.
authors.affiliation: FM Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, University of Pennsylvania Scheie Eye Institute, Stellar-Chance Laboratories, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Mahasweta
authors.initials: M
authors.lastname: Dutt
authors.forename: Philomela
authors.initials: P
authors.lastname: Tabuena
authors.forename: Elvira
authors.initials: E
authors.lastname: Ventura
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Shindler
mesh_terms: D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000008:administration & dosage; D051379:Mice; D009902:Optic Neuritis / Q000188:drug therapy* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D013266:Stilbamidines; D003907:Dexamethasone; D008775:Methylprednisolone