Calpain and N-methyl-d-aspartate (NMDA)-induced excitotoxicity in rat retinas.
Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death in both acute insults and the chronic neurodegenerative disorders in the central nerves system. However, activation of calpain also plays a protective function in the early phase of excitotoxic neuronal death. The exact role of calpains in neuronal death and recovery after exposure to N-methyl-D-aspartate (NMDA) is not clearly known. The purpose of present study was to examine the involvement of mu- and m-calpain in NMDA-induced excitotoxicity in the adult rat retina. Increased immunoreactivity of mu-calpain was noted in RGC layer cells and in the inner nuclear layer with maximal expression at 12 h after NMDA injection. This was further confirmed with Western blotting. TdT-mediated biotin-dUTP nick end labeling (TUNEL) positive cells in the inner retina co-localized with moderate or intense mu-calpain immunoreactivity. In contrast, there was no remarkable change in m-calpain immunoreactivity at any time point after NMDA injection. Simultaneous injection of 2 nmol of a calpain inhibitor (calpain inhibitor II) significantly reduced the number of TUNEL-positive cells in the inner retina at 18 h after NMDA injection and preserved RGC-like cells counted at 7 days after injection. The results of this study showed that mu-calpain may be involved in mediating NMDA-induced excitotoxicity in the rat retina and calpain inhibitors may play a therapeutic role in NMDA related disease.
Chiu
Kin
K
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong.
Lam
Tim Tak
TT
Ying Li
Winnie Wai
WW
Caprioli
Joseph
J
Kwong Kwong
Jacky Man
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes; D008297:Male; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000201:enzymology*
D007527:Isoenzymes; D009498:Neurotoxins; D016202:N-Methylaspartate; D002154:Calpain; C449000:m-calpain; C449002:mu-calpain