Broad spectrum caspase inhibitor rescues retinal ganglion cells after ischemia.
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.
Patil
Kiran
K
Department of Ophthalmology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Sharma
Sansar C
SC
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020169:Caspases