TY - JOUR
T1 - Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina
AU - Sakamoto, Y.
AU - Nakajima, T.
AU - Fukiage, C.
AU - Sakai, O.
AU - Yoshida, Y.
AU - Azuma, M.
AU - Shearer, T. R.
N1 - Funding Information:
Partially supported by NIH grant EY05786 to TRS.
PY - 2000
Y1 - 2000
N2 - Purpose. Much evidence has accumulated suggesting that activation of calpain causes neuronal cell death in ischemic brain. However, little is known about the involvement of calpain in retinal cell death in ischemic injury. Thus, the purpose of present study was to investigate the involvement of calpain isoforms (m-and μ-calpain) in ischemia-reperfusion injury in retina from rat. Methods. Retinal ischemia was produced by occlusion of the central retinal artery for one hour, and this was followed by reperfusion for seven days. Calpain mRNAs, calpain activities, total calcium content and proteolysis of α-spectrin were determined in retina. Effect of a calpain inhibitor SJA6017 was histologically tested in retinal injury after ischemia-reperfusion. Results. Following retinal ischemia, most of cells in the ganglion cell layer were sloughed off by day 1 after reperfusion, followed by loss of cells in the inner plexiform layer on day 3 and loss of cells in the inner nuclear layer by day 5. These morphologic changes were accompanied by several presumptive biochemical indicators of calpain activation: increased calcium, proteolysis of α-spectrin (a sensitive substrate for calpains), decreased caseinolytic activity for both calpains (suggesting calpain activation followed by autolytic degradation), increased mRNA levels for μ-calpain and calpastatin - the endogenous inhibitor of calpains - and decreased mRNA levels for μ-calpain. Moreover, the calpain inhibitor SJA6017 protected the reduction of cell density in the ganglion cell layer after ischemia-reperfusion. Conclusion. These results suggest that calpain isoforms may play an important role in neuronal cell death induced by retinal ischemia-reperfusion injury in rat.
AB - Purpose. Much evidence has accumulated suggesting that activation of calpain causes neuronal cell death in ischemic brain. However, little is known about the involvement of calpain in retinal cell death in ischemic injury. Thus, the purpose of present study was to investigate the involvement of calpain isoforms (m-and μ-calpain) in ischemia-reperfusion injury in retina from rat. Methods. Retinal ischemia was produced by occlusion of the central retinal artery for one hour, and this was followed by reperfusion for seven days. Calpain mRNAs, calpain activities, total calcium content and proteolysis of α-spectrin were determined in retina. Effect of a calpain inhibitor SJA6017 was histologically tested in retinal injury after ischemia-reperfusion. Results. Following retinal ischemia, most of cells in the ganglion cell layer were sloughed off by day 1 after reperfusion, followed by loss of cells in the inner plexiform layer on day 3 and loss of cells in the inner nuclear layer by day 5. These morphologic changes were accompanied by several presumptive biochemical indicators of calpain activation: increased calcium, proteolysis of α-spectrin (a sensitive substrate for calpains), decreased caseinolytic activity for both calpains (suggesting calpain activation followed by autolytic degradation), increased mRNA levels for μ-calpain and calpastatin - the endogenous inhibitor of calpains - and decreased mRNA levels for μ-calpain. Moreover, the calpain inhibitor SJA6017 protected the reduction of cell density in the ganglion cell layer after ischemia-reperfusion. Conclusion. These results suggest that calpain isoforms may play an important role in neuronal cell death induced by retinal ischemia-reperfusion injury in rat.
KW - Calpain
KW - Calpain inhibitor SJA6017
KW - Ischemia-reperfusion
KW - Rat
KW - Retina
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U2 - 10.1076/0271-3683(200007)2111-ZFT571
DO - 10.1076/0271-3683(200007)2111-ZFT571
M3 - Article
C2 - 11035539
AN - SCOPUS:0033749658
SN - 0271-3683
VL - 21
SP - 571
EP - 580
JO - Current Eye Research
JF - Current Eye Research
IS - 1
ER -