Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice

Masato Koike, Masahiro Shibata, Yoshiyuki Ohsawa, Hiroshi Nakanishi, Tomoyuki Koga, Satoshi Kametaka, Satoshi Waguri, Takashi Momoi, Eiki Kominami, Christoph Peters, Kurt Von Figura, Paul Saftig, Yasuo Uchiyama

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)146-161
Number of pages16
JournalMolecular and Cellular Neuroscience
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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