Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina

Y. Sakamoto, T. Nakajima, C. Fukiage, O. Sakai, Y. Yoshida, M. Azuma, T. R. Shearer

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalCurrent Eye Research
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2000

Keywords

  • Calpain
  • Calpain inhibitor SJA6017
  • Ischemia-reperfusion
  • Rat
  • Retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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