Compound 49b Reduces Inflammatory Markers and Apoptosis after Ocular Blast Injury

Abstract

In year 2 of this project, we determined whether Compound 49b, a novel beta-adrenergic receptor agonist, prevented increased inflammatory and apoptosis proteins in insulin-like growth factor binding protein 3 (IGFBP-3) knockout (KO) mice after exposure to ocular blast. Eyes from IGFBP-3 KO mice were exposed to a blast of air from a paintball gun at 26psi. Eyes were collected at 4, 24, and 72 hours after blast exposure. In a subset of mice, Compound 49b eye drops (1mM dose) were applied within 4 hours, 24 hours, or 72 hours after blast. Three days after exposure to blast, all mice were sacrificed. One eye was used for protein analyses of TNF , IL-1 , Bax, Bcl-xL, caspase 3, and cytochrome C. We found that ocular exposure to 26psi of air pressure led to a significant increase in both inflammatory and apoptotic proteins. When Compound 49b was applied within 4 or 24 hours after blast, it mitigated the increase in inflammatory and apoptotic proteins. Ocular blast produces a significant increase in inflammatory and apoptotic proteins in the retina, specifically in retinal ganglion cells. These proteins are reduced after treatment with a topical beta-adrenergic receptor agonist. This data suggests local application of beta-adrenergic receptor agonists may be protective in ocular blast.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2014
Accession Number
ADA612557

Entities

People

  • Jena J. Steinle

Organizations

  • University of Tennessee

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Blast Injuries
  • Brain
  • Brain Injuries
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Department Of Defense
  • Endothelial Cells
  • Explosives
  • Eye Injuries
  • Growth Factors
  • Improvised Explosive Devices
  • Ophthalmology
  • Proteins
  • Retinal Diseases
  • Wounds And Injuries

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Explosive Engineering.
  • Neurotrauma and Rehabilitation Medicine.