Iron-induced cytotoxicity in cultured rat retinal neurons.
Oxidative stress has been proposed as a major injury mechanism in the central nervous system including the retina. In this study, as an initial attempt to study the mechanism of oxidative injury in the retina, we developed a cell culture model by utilizing the iron exposure paradigm. Exposure of rat retinal cultures for 24 hours to 10-40 MicroM ferrous or ferric chloride induced a concentration-dependent death of retinal neurons but not of photoreceptors or astrocytes. An antioxidant, trolox effectively attenuated the iron-induced death of neurons and photoreceptors in a dose-dependent manner whereas neither glutamate receptor antagonists nor cycloheximide were protective. Of retinal interneurons, GABAergic neurons were more vulnerable to the iron toxicity than calbindin (+) horizontal neurons. These findings show that iron exposure induces anti-oxidant-sensitive neuronal injury in retinal culture, independent of the excitotoxic or the apoptotic mechanisms. Of retinal neurons, different cell types exhibit differential vulnerabilities to the iron-induced oxidative injury. This simplified culture model system may be useful in elucidating mechanisms of oxidative injury in the retina.
Sohn
J
J
Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yoon
Y H
YH
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects; D002712:Chlorides; D053938:DNA Fragmentation / Q000187:drug effects; D005290:Ferric Compounds / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000378:metabolism; D018384:Oxidative Stress; D010784:Photomicrography; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002712:Chlorides; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005680:gamma-Aminobutyric Acid; C024555:ferric chloride