title: Compound 49b protects against blast-induced retinal injury.
abstract: OBJECTIVE
  To determine whether Compound 49b, a novel beta-adrenergic receptor agonist, can prevent increased inflammation and apoptosis in mice after exposure to ocular blast.
  
  
  METHODS
  Eyes of C57/BL6 mice were exposed to a blast of air from a paintball gun at 26 psi (≈0.18 MPa). Eyes were collected 4 hours, 24 hours, and 72 hours after blast exposure. In a subset of mice, Compound 49b eyedrops (1 mM) were applied within 4 hours, 24 hours, or 72 hours of the blast. Three days after blast exposure, all mice were sacrificed. One eye was used to measure levels of retinal proteins (TNFα, IL-1β, Bax, BcL-xL, caspase 3, and cytochrome C). The other eye was used for TUNEL labeling of apoptotic cells, which were co-labeled with NeuN to stain for retinal ganglion cells.
  
  
  RESULTS
  We found that ocular exposure to 26 psi air pressure led to a significant increase in levels of apoptotic and inflammatory mediators within 4 hours, which lasted throughout the period investigated. When Compound 49b was applied within 4 hours or 24 hours of blast injury, levels of apoptotic and inflammatory mediators were significantly reduced. Application of Compound 49b within 72 hours of blast injury reduced levels of inflammatory mediators, but not to untreated levels.
  
  
  CONCLUSIONS
  Ocular blast injury produces a significant increase in levels of key inflammatory and apoptotic markers in the retina as early as 4 hours after blast exposure. These levels are significantly reduced if a beta-adrenergic receptor agonist is applied within 24 hours of blast exposure. Data suggest that local application of beta-adrenergic receptor agonists may be beneficial to reduce inflammation and apoptosis.
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, 930 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Youde
authors.initials: Y
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Pagadala
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
authors.forename: Jena J
authors.initials: JJ
authors.lastname: Steinle
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D001753:Blast Injuries / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000008:administration & dosage*; D012160:Retina / Q000187:drug effects* / Q000293:injuries*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D000318:Adrenergic beta-Agonists; D009883:Ophthalmic Solutions
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