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T Kurimoto, T Miyoshi, M Watanabe, O Mimura, Y Fukuda; Apoptotic Cell Death of Beta Cells After Optic Nerve Transection in Adult Cat Retinas . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2185.
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Purpose: We have previously reported on axotomized cat retinal ganglion cells that survival rate of beta cells rapidly decreased down to 29% from day 3 to 7, whereas that of alpha cells remained 64% even day 14 after optic nerve transection (Watanabe et al, 2001). In the present study, we asked whether or not the rapid phase of beta cell death after axotomy is attributable to apoptosis. Methods: Under deep anesthesia the optic nerve was completely sectioned on one side in adult cats as we have done previously (Watanabe et al, 2001). The following two series of experiments were done. 1) Whole-mounted retinas from 3 to 14 days after axotomy were Nissl-stained with 0.1% cresyl violet. Pyknotic cells characterized with nuclear chromatin condensation were counted at three different regions for each retina; area centralis (AC), 3mm temporal from AC on horizontal line, and midpoint between AC and optic disk. 2) Survival-promoting effect of intraocularly-applied caspase 3 inhibitor (z-DEVD-cmk,500µg) was estimated for alpha and beta cells on day 7 after axotomy by means of retrograde labelling and intracellular injection of Lucifer Yellow. Results: 1) In Nissl-stained whole mounted retinas, pyknotic cells started to appear on day 3 after axotomy. The proportion of pyknotic cells gradually increased from day 4, reached a maximum on day 6 (average 16.4%, at AC) and decreased after day 7; the time course roughly corresponds to that of rapid death of axotomized beta cells. The proportion of pyknotic cells was highest at AC, where beta cells were densely distributed, among the three retinal regions examined. 2) Intraocular application of z-DEVD-cmk significantly increased the survival rate of axotomized beta cells but not that of alpha cells. (see Figure)Conclusions: These results suggest that the rapid death of beta cells after optic nerve transection is mainly due to apoptosis which is mediated by caspase 3 and that slow death of beta cells may be attributed to some other mechanism. View OriginalDownload SlideView OriginalDownload Slide
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