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The Journal of Neuroscience, May 15, 2003, 23(10):4023-4028

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Apoptotic Death of Cells after Optic Nerve Transection in Adult Cats

Takuji Kurimoto,^1,2 Tomomitsu Miyoshi,¹ Akira Suzuki,¹ Toru Yakura,¹ Masami Watanabe,³ Osamu Mimura,² and Yutaka Fukuda¹

¹Department of Physiology and Biosignaling, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan, ²Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, and ³Department of Physiology, Institute for Developmental Research, Kasugai, Aichi 480-0392, Japan

We have revealed previously that the survival rate of cells of cat retinal ganglion cells (RGCs) rapidly decreased to 29% on day 7 after optic nerve transection, whereas that of cells slowly decreased to 64% on day 14 (Watanabe et al., 2001). The reason that cells die more rapidly than cells was not clear. In the present study, we tested the possibility that the rapid death of cells is attributable to apoptosis, as shown for some axotomized RGCs in rats. The following results were obtained. First, the proportion of pyknotic cells in Nissl-stained cat retinas started to increase sharply starting on day 4 and reached a peak on day 6 after optic nerve transection. The time course of occurrence of pyknotic cells corresponded well with that of the rapid death of axotomized cells. Secondly, the proportion of pyknotic cells was the highest in the area centralis (AC), in which cells are densely distributed. The preferential death of axotomized RGCs in the AC was also confirmed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in cross sections. Thirdly, after the intravitreal injection of caspase 3 inhibitor (Z-DEVD-cmk) the survival of axotomized cells on day 7 was significantly enhanced, whereas no such survival-promoting effect was obtained in axotomized cells. Taken together, these results suggest that the rapid death of axotomized cells is attributable mainly to apoptosis, which is mediated by caspase 3.

Key words: adult cat; retinal ganglion cells; cells; optic nerve transection; apoptosis; caspase 3 inhibitor

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Received Sep. 25, 2002; revised Mar. 3, 2003; accepted Mar. 5, 2003.

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