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Gülgün Tezel, Martin B. Wax; Inhibition of Caspase Activity in Retinal Cell Apoptosis Induced by Various Stimuli In Vitro. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2660-2667.
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purpose. Although recent work implicates a decisive role for a family of
cysteine aspartic acid proteases, termed caspases, as mediators of
neuronal apoptosis, little is known about caspase activation that
accompanies apoptosis in the retina. The purpose of this study was to
investigate caspase activation in retinal cell apoptosis induced by
various stimuli, including simulated ischemia, excitotoxicity, and
antibody to heat shock protein 27 (hsp27), and to assess whether the
inhibition of caspases can block apoptosis in retinal cells induced by
methods. Apoptotic cell death induced in cultured retinal cells by simulated
ischemia, excitotoxicity, or hsp27 antibody was examined by terminal
deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique.
Changes in the caspase activity were studied using western blot
analysis and a fluorometric protease activity assay in the presence or
absence of caspase inhibitors. In addition, changes in the expression
of bcl-2 and bax were examined by western blot analysis.
results. The authors’ in vitro observations revealed that the apoptotic process
in retinal cells induced by different stimuli share a common
executioner proteolysis cascade, including caspase-3 and poly-(ADP
ribose) polymerase cleavage. One exception, however, was that caspase-8
activation was only observed during the apoptosis induced by hsp27
antibody. In retinal cells going to apoptosis regardless of the
stimulus, bcl-2 expression was decreased and bax expression was
increased. Furthermore, the authors observed that treatment of retinal
cells with inhibitors of caspases, including B-D-FMK and Z-IETD-FMK,
blocked the apoptotic cell death induced by different stimuli.
conclusions. The authors’ observations provide a better understanding of the
apoptotic process in retinal cells at molecular level and demonstrate
an effective blockade of caspase activation with specific inhibitors.
These findings may have therapeutic implications in the treatment of
neuroretinal diseases, which are characterized by apoptotic cell
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