Apoptotic death of β cells after optic nerve transection in adult cats

Abstract

We have revealed previously that the survival rate of β cells of cat retinal ganglion cells (RGCs) rapidly decreased to 29% on day 7 after optic nerve transection, whereas that of α cells slowly decreased to 64% on day 14 (Watanabe et al., 2001). The reason that β cells die more rapidly than a cells was not clear. In the present study, we tested the possibility that the rapid death of β 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 β cells. Secondly, the proportion of pyknotic cells was the highest in the area centralis (AC), in which β 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 β cells on day 7 was significantly enhanced, whereas no such survival-promoting effect was obtained in axotomized α cells. Taken together, these results suggest that the rapid death of axotomized β cells is attributable mainly to apoptosis, which is mediated by caspase 3.