[HPETE, an arachidonic acid metabolite, induces apoptosis in rat retina in vitro].
BACKGROUND
Apoptosis is a gene-regulated mode of cell death which gains increasing importance in retinal pathologies such as retinitis pigmentosa, retinal detachment and proliferative vitreoretinopathy. A better understanding of the regulation of apoptosis could imply the means to reduce photoreceptor cell death and thereby provide therapeutic strategies to influence the time course of retinal diseases. Previous studies in our laboratory demonstrated that light induces apoptosis in the rat retina in vivo as a function of light dose. In several cell systems, oxidative stress including oxygenated metabolites of arachidonic acid (AA) was found to evoke apoptosis. We have observed a light-elicited release of AA and the subsequent formation of its metabolites in the rat retina. Therefore, AA and its metabolites appeared to be suitable candidates for the induction of apoptosis during light exposure.


METHODS
Isolated rat retinas were incubated for 60, 120 and 180 min, respectively, with and without the addition of 30 mumol 5S-hydroperoxyeicosatetraenoic acid (5-HPETE). Retinas were then processed for light- and electron microscopy and examined for the morphological signs of apoptosis. The rate of apoptosis in the outer nuclear layer was assessed quantitatively.


RESULTS
5S-HPETE induces apoptosis of photoreceptors in the rat retina in vitro. Quantitative analysis revealed a significant increase in the rate of apoptosis of 5S-HPETE-treated retinas when compared to untreated controls.


CONCLUSIONS
Arachidonic acid metabolites released upon light exposure may represent messenger candidates for apoptosis in the retina.
Universitäts-Augenklinik Zürich, Labor für Zellbiologie der Netzhau.
F
F
Hafezi
J J
JJ
Reinboth
A
A
Wenzel
K
K
Munz
C E
CE
Remé
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000502:physiology*; D008854:Microscopy, Electron; D010865:Pilot Projects; D051381:Rats; D012160:Retina / Q000473:pathology*
D015289:Leukotrienes; D016718:Arachidonic Acid; C025348:arachidonic acid 5-hydroperoxide