Caspase inhibitors protect against NMDA-mediated retinal ganglion cell death
Standard
Caspase inhibitors protect against NMDA-mediated retinal ganglion cell death. / Schuettauf, Frank; Stein, Thomas; Choragiewicz, Tomasz J; Rejdak, Robert; Bolz, Sylvia; Zurakowski, David; Varde, Meghana A; Laties, Alan M; Thaler, Sebastian.
In: CLIN EXP OPHTHALMOL, Vol. 39, No. 6, 08.2011, p. 545-54.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Caspase inhibitors protect against NMDA-mediated retinal ganglion cell death
AU - Schuettauf, Frank
AU - Stein, Thomas
AU - Choragiewicz, Tomasz J
AU - Rejdak, Robert
AU - Bolz, Sylvia
AU - Zurakowski, David
AU - Varde, Meghana A
AU - Laties, Alan M
AU - Thaler, Sebastian
N1 - © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.
PY - 2011/8
Y1 - 2011/8
N2 - BACKGROUND: Apoptosis is a major mechanism of cell death in glutamate-induced excitotoxicity and caspases as the executors of apoptosis play an important role in the development of various central nervous system and eye diseases. We studied the involvement of certain caspases in excitotoxic retinal ganglion cell death, which was experimentally induced in Brown Norway Rats by application of the glutamate receptor agonist N-methyl-D-aspartate (NMDA).METHODS: Animals were injected intravitreally with one of six caspase inhibitors (against caspases 1, 3, 4, 6, 8 and 9). Seven hours later, NMDA or phosphate-buffered saline as a control was injected intravitreally into the respective eyes. The neuroprotective potential against NMDA toxicity was assessed by retinal ganglion cell quantification. Additionally, wholemount TUNEL was performed.RESULTS: Statistical analysis revealed significant neuroprotective effects for the inhibitors of caspases 3, 6, 8 and 9, but not for those of caspases 1 and 4. The inhibitors of caspases 6 and 9 showed greater neuroprotective potential than those of caspases 3 and 8, although cell death was not entirely averted in any case. Results of ganglion cell counts were confirmed for the most pronounced treatment groups using wholemount TUNEL.CONCLUSION: Excitotoxic retinal ganglion cell death after NMDA injection is mediated mainly through apoptosis, whereby extrinsic as well as intrinsic pathways of caspase activation play a role.
AB - BACKGROUND: Apoptosis is a major mechanism of cell death in glutamate-induced excitotoxicity and caspases as the executors of apoptosis play an important role in the development of various central nervous system and eye diseases. We studied the involvement of certain caspases in excitotoxic retinal ganglion cell death, which was experimentally induced in Brown Norway Rats by application of the glutamate receptor agonist N-methyl-D-aspartate (NMDA).METHODS: Animals were injected intravitreally with one of six caspase inhibitors (against caspases 1, 3, 4, 6, 8 and 9). Seven hours later, NMDA or phosphate-buffered saline as a control was injected intravitreally into the respective eyes. The neuroprotective potential against NMDA toxicity was assessed by retinal ganglion cell quantification. Additionally, wholemount TUNEL was performed.RESULTS: Statistical analysis revealed significant neuroprotective effects for the inhibitors of caspases 3, 6, 8 and 9, but not for those of caspases 1 and 4. The inhibitors of caspases 6 and 9 showed greater neuroprotective potential than those of caspases 3 and 8, although cell death was not entirely averted in any case. Results of ganglion cell counts were confirmed for the most pronounced treatment groups using wholemount TUNEL.CONCLUSION: Excitotoxic retinal ganglion cell death after NMDA injection is mediated mainly through apoptosis, whereby extrinsic as well as intrinsic pathways of caspase activation play a role.
KW - Animals
KW - Apoptosis/drug effects
KW - Caspase Inhibitors
KW - Cell Count
KW - Cell Survival
KW - Cytoprotection
KW - Enzyme Inhibitors/pharmacology
KW - Excitatory Amino Acid Agonists/toxicity
KW - Female
KW - In Situ Nick-End Labeling
KW - Intravitreal Injections
KW - N-Methylaspartate/toxicity
KW - Rats
KW - Rats, Inbred BN
KW - Rats, Long-Evans
KW - Retinal Ganglion Cells/drug effects
U2 - 10.1111/j.1442-9071.2010.02486.x
DO - 10.1111/j.1442-9071.2010.02486.x
M3 - SCORING: Journal article
C2 - 21176044
VL - 39
SP - 545
EP - 554
JO - CLIN EXP OPHTHALMOL
JF - CLIN EXP OPHTHALMOL
SN - 1442-6404
IS - 6
ER -