title: Calpain inhibition attenuates apoptosis of retinal ganglion cells in acute optic neuritis.
abstract: OBJECTIVE
  Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with the pathogenesis of multiple sclerosis (MS) and is initiated by the attack of autoreactive T cells against self-myelin antigens, resulting in demyelination, degeneration of retinal ganglion cells (RGCs), and cumulative visual impairment.
  
  
  METHODS
  Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats on day 0, and animals received daily intraperitoneal injections of calpain inhibitor (calpeptin) or vehicle from day 1 until killed. Retinal cell death was analyzed by DNA fragmentation, and surviving ganglion cells were quantified after double labeling of retinal tissue with TUNEL and Brn3a. The expression of apoptotic and inflammatory proteins was determined by Western blotting.
  
  
  RESULTS
  It was demonstrated that calpain inhibition downregulates expression of proapoptotic proteins and the proinflammatory molecule nuclear factor-kappa B (NF-κB) in the retina of Lewis rats with acute EAE. Immunofluorescent labeling revealed that apoptotic cells in the RGC layer of vehicle-treated EAE animals were Brn3a positive, and a moderate dose of calpeptin dramatically reduced the frequency of apoptotic RGCs.
  
  
  CONCLUSIONS
  These results suggest that calpain inhibition might be a useful supplement to immunomodulatory therapies such as corticosteroids in ON, due to its neuroprotective effect on RGCs.
authors: Departments of Neurosciences, Division of Neurology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors: Amena W
authors: AW
authors: Smith
authors: Arabinda
authors: A
authors: Das
authors: M Kelly
authors: MK
authors: Guyton
authors: Swapan K
authors: SK
authors: Ray
authors: Baerbel
authors: B
authors: Rohrer
authors: Naren L
authors: NL
authors: Banik
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