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Naomichi Katai, Nagahisa Yoshimura; Apoptotic Retinal Neuronal Death by Ischemia–Reperfusion Is Executed by Two Distinct Caspase Family Proteases. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2697-2705.
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purpose. To evaluate possible roles of caspase-1 and caspase-3 in retinal
methods. Retinal ischemia was induced in rats by increasing the intraocular
pressure to 110 mm Hg for 60 minutes. Expression of caspase-1 and
caspase-3 was studied at the mRNA and protein levels using
immunohistochemical staining, western blot analysis, semiquantitative
reverse transcription–polymerase chain reaction, and assay of the
enzymatic activities. Apoptotic retinal neurons were detected by the
TdT-dUTP terminal nick-end labeling (TUNEL) method. To study the roles
of the caspases in retinal ischemia–reperfusion injury, an inhibitor
of caspase-1, acetyl-tyrosyl-valyl-alanyl-aspart-1-al (Ac-YVAD-CHO;
total dose, 10−7 moles) and that of caspase-3,
acetyl-aspartyl-glutamyl-valyl-aspart1-al (Ac-DEVD-CHO; total dose,
10−7 moles) was injected intravitreally and the number of
TUNEL-positive cells was compared with the number in sections not
treated with the inhibitors.
results. In the inner nuclear layer (INL), caspase-3-like immunoreactivity was
predominantly detected, whereas caspase-1-like immunoreactivity was
more predominant in the outer nuclear layer (ONL). Expression of
caspase-1 and -3 was upregulated at the protein and gene levels 24
hours after reperfusion. Intravitreal injection of Ac-DEVD-CHO
decreased the number of TUNEL-positive cells more significantly in the
INL than in the ONL (P < 0.01) at 24 hours,
whereas, intravitreal injection of Ac-YVAD-CHO was more effective in
decreasing the number in the ONL (P < 0.05).
conclusions. These findings suggest a possibility that cell-type–specific
activation of caspases takes place in retinal ischemia–reperfusion
injury, and such caspase may induce retinal neuronal cell
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