title: Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision restoration after rabbit traumatic optic nerve injury.
abstract: OBJECTIVE
  Vision loss after traumatic optic nerve injury is considered irreversible because of the retrograde loss of retinal ganglion cells (RGCs) which undergo apoptosis. Because the second messenger caspase-3 plays a major role in apoptosis, we now evaluated the efficacy of the specific caspase-3 inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which mimics traumatic optic nerve injury in humans to enhance cell survival and improve vision.
  
  
  METHODS
  Survival of RGCs and recovery of vision were studied using retinal morphological markers and visual evoked potentials (VEP), respectively. The FPI traumatized animals were treated in their right eye with a single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury compared to 2% DMSO control injections in their left eye.
  
  
  RESULTS
  Intravitreal Z-DEVD-FMK, but not control injections, led to down-regulation of capase-3 and reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post-injury. These morphological improvements were accompanied by vision restoration as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD-FMK was more effective than the peribulbar application.
  
  
  CONCLUSIONS
  The caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans.
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Medical Psychology, Medical Faculty, Otto.-v.-Guericke University of Magdeburg, Magdeburg, Germany.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005074:Evoked Potentials, Visual / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010775:Photic Stimulation; D011817:Rabbits; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D053148:Caspase 3
keywords: Caspase-3 inhibitor; apoptosis; neuroprotection; optic nerve injury; vision restoration