Decreased retinal neuronal cell death in caspase-1 knockout mice.
OBJECTIVE
To determine whether apoptosis of retinal neurons induced by excessive light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout mice.


METHODS
Eight- to 10-week-old caspase-1 knockout mice (Casp1-/-) and wild-type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light of 25,000 lux for 2 h. Other mice were subjected to retinal ischemia by increasing the intraocular pressure to 110 mmHg for 45 min. Electroretinograms (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick-end labeling (TUNEL) was performed to identify the apoptotic cells after the insults. The inner retinal thickness was measured to evaluate the retinal injury after the ischemia-reperfusion. Expression of caspase-1 protein was studied by immunohistochemical analysis and Western blotting. Caspase-1-like protease activity was determined by a colorimetric tetrapeptide substrate.


RESULTS
The morphology of the retina and the amplitudes of the a and b waves of the ERGs of Casp1-/- mice did not differ from those of WT mice. After the light exposure, TUNEL-positive cells were observed in the outer nuclear layer of the WT mice retina. The number of TUNEL-positive photoreceptor nuclei after the light exposure, and the number of nuclei in the inner nuclear layer after the ischemia-reperfusion injury, were significantly less in Casp1-/- mice than in WT mice. There were more caspase-1-positive photoreceptor cells in WT mice after the light injury. The inner retinal layer of Casp1-/- mice was significantly thicker in Casp1-/- mice than in WT mice 2 weeks after the ischemic insult.


CONCLUSIONS
Retinal neuronal apoptosis was less prominent in Casp1-/- mice after excessive light exposure and ischemia-reperfusion injury. These data indicate that caspase-1 plays a role in retinal neuronal apoptosis.
Arai
Jun
J
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
Katai
Naomichi
N
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan. katainao@hsp.md.shinshu-u.ac.jp.
Kuida
Keisuke
K
Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts, USA.
Kikuchi
Takanobu
T
Research Support Center for Human and Environmental Sciences, Shinshu University, Matsumoto, Japan.
Yoshimura
Nagahisa
N
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012160:Retina / Q000166:cytology* / Q000378:metabolism
D004247:DNA; D020170:Caspase 1