DNA fragmentation characteristic of apoptosis and cell loss induced by kainic acid in rabbit retinas
We have examined whether in vivo exposure to the glutamate analogue, kainic acid, induces cell loss through apoptosis and/or through necrosis. The vulnerability of rabbit retinal cells was evaluated by routine histopathology. The DNA fragmentation was examined using an in situ method (TUNEL: TdT-med...
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Published in | Neurochemistry international Vol. 31; no. 2; pp. 251 - 260 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.08.1997
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | We have examined whether
in vivo exposure to the glutamate analogue, kainic acid, induces cell loss through apoptosis and/or through necrosis. The vulnerability of rabbit retinal cells was evaluated by routine histopathology. The DNA fragmentation was examined using an
in situ method (TUNEL: TdT-mediated biotin-dUTP nick-end labelling) and agarose gel electrophoresis of extracted retinal DNA. Retinas were examined at 30
min, and 4, 16, 24 and 36
h, and 2–5
days following the intraocular administration of 140
nmol kainic acid.
Although pyknotic cells could be seen already at 30
min post-injection, TUNEL-labelled nuclei were first observed 4
h after the injection. A relatively large number of pyknotic cells and of TUNEL-labelled nuclei were still seen at 5
days post-injection. Pyknotic cells were seen throughout the inner nuclear layer (mostly in the proximal half of the layer) and in the ganglion cell layer. The TUNEL-labelled nuclei were almost only seen in the proximal inner nuclear layer. Analysis of DNA by electrophoresis revealed the presence of large molecular weight fragments 4
h after the injection, and of oligonucleosome-size fragments between 16
h and 2
days after the injection.
The present study thus presents evidence that, in our model, the retinal cell loss induced by kainic acid is preceded, probably in most cells, by a fragmentation of DNA characteristic of apoptotic cell death. The process of cell loss following kainic acid administration was found to be relatively slow, further suggesting that a programmed type of cell death, which eventually induces apoptosis, is involved. No indication that cells were lost also through necrosis was obtained. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0197-0186 1872-9754 |
DOI: | 10.1016/S0197-0186(96)00156-8 |