Broad spectrum caspase inhibitor rescues retinal ganglion cells after ischemia

Neuroreport. 2004 Apr 29;15(6):981-4. doi: 10.1097/00001756-200404290-00010.

Abstract

Following ischemia/reperfusion the death of retinal ganglion cells in adult Wistar rat retina continues for weeks. Using new, more stable caspase inhibitor, Q-VD-OPH we studied its neuroprotective effect on identifiable retinal ganglion cells after 75 min ischemia followed by reperfusion. Q-VD-OPH was injected intravitreally 48 h after ischemia/reperfusion. Retinal ganglion cells were labeled by intratectal injection of Fluorogold and cells were counted on flat mounted retinas. Retinal ganglion cells survival increased after 2 and 3 weeks of ischemia/reperfusion in Q-VD-OPH injected eyes. We studied apoptotic cell death by immunocytochemically labeling retina with cleaved Poly (ADP-ribose) polymerase (PARP). Labeling for cleaved PARP remained elevated in the ganglion cell layer and inner nuclear layer after 1,2and 3 weeks of ischemia/reperfusion. Administration of Q-VD-OPH significantly reduced the labeling for cleaved PARP in the retina and increased the survival of retinal ganglion cells.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caspase Inhibitors*
  • Caspases / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Ischemia / drug therapy*
  • Ischemia / enzymology
  • Rats
  • Rats, Wistar
  • Retina / drug effects
  • Retina / enzymology
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / enzymology

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Caspases