TY - JOUR
T1 - Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice
AU - Koike, Masato
AU - Shibata, Masahiro
AU - Ohsawa, Yoshiyuki
AU - Nakanishi, Hiroshi
AU - Koga, Tomoyuki
AU - Kametaka, Satoshi
AU - Waguri, Satoshi
AU - Momoi, Takashi
AU - Kominami, Eiki
AU - Peters, Christoph
AU - Von Figura, Kurt
AU - Saftig, Paul
AU - Uchiyama, Yasuo
N1 - Funding Information:
This work was supported by Grant-in-Aids on Priority Areas from Japan Society for the Promotion of Science (Y.U., S.W.), Grant-in-Aid for Japan Society for the Promotion of Science Fellows (M.K.), and Deutsche Forschungsgemeinschaft.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - To understand the mechanisms of retinal atrophy in cathepsin D-deficient mice, the postnatal development of their retinae was analyzed. TUNEL-positive cells appeared abundantly in the outer nuclear layer (ONL) and slightly in the inner nuclear layer (INL). Nitric oxide synthase (NOS) was induced in microglial cells which invaded retinal layers and phagocytosed dead cell debris, while NOS inhibitors prevented cell death in the INL but not in the ONL. Caspases 9 and 3 were activated only in the ONL after P15. Moreover, no atrophic change was detected in the retina of mice deficient in cathepsin B or L. These results suggest that cathepsin D is essential for the metabolic maintenance of retinal photoreceptor cells and that its deficiency induces apoptosis of the cells, while the loss of INL neurons is mediated by NO from microglial cells.
AB - To understand the mechanisms of retinal atrophy in cathepsin D-deficient mice, the postnatal development of their retinae was analyzed. TUNEL-positive cells appeared abundantly in the outer nuclear layer (ONL) and slightly in the inner nuclear layer (INL). Nitric oxide synthase (NOS) was induced in microglial cells which invaded retinal layers and phagocytosed dead cell debris, while NOS inhibitors prevented cell death in the INL but not in the ONL. Caspases 9 and 3 were activated only in the ONL after P15. Moreover, no atrophic change was detected in the retina of mice deficient in cathepsin B or L. These results suggest that cathepsin D is essential for the metabolic maintenance of retinal photoreceptor cells and that its deficiency induces apoptosis of the cells, while the loss of INL neurons is mediated by NO from microglial cells.
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U2 - 10.1016/S1044-7431(03)00035-6
DO - 10.1016/S1044-7431(03)00035-6
M3 - Article
C2 - 12676526
AN - SCOPUS:0037301337
SN - 1044-7431
VL - 22
SP - 146
EP - 161
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 2
ER -