Mechanism of Hypoxia-Induced Cytotoxicity in Cultured Rat Retinal Neurons.
- Author:
Young Hee YOON
1
;
Jaeheung LEE
Author Information
1. Department of Ophthalmology, Ulsan University, College of Medicinem Asan Medical Center, Seoul,Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
Cultured retinal neurons;
Excitotoxicity;
Free radical injury;
Hypoxia-ischemia
- MeSH:
Animals;
Anoxia;
Apoptosis;
Buthionine Sulfoximine;
Cell Death;
Cycloheximide;
Dizocilpine Maleate;
Excitatory Amino Acid Antagonists;
Glutathione;
In Situ Nick-End Labeling;
Masks;
Necrosis;
Neurons;
Rats*;
Retinal Neurons*;
Retinaldehyde*
- From:Journal of the Korean Ophthalmological Society
1997;38(11):1975-1986
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Retinal neurons are highly vulnerable to hypoxia/ischemia. Excitotoxicity and free radical injury have been proposed as the major mechanisms of ischemic retinal injury have been proposed as the major mechanisms of ischemic retinal neuronal death. In the present study, we examined these possibilities in retinal cultures. Exposure of these cultures to hypoxia for 48 hr induced selective death of neurons. Addition of an antioxidiant trolox markedly attenuated hypoxiainduced retinal neuronal death, whereas addition of glutamate antagonists, MK-801 or CNQX,did not. Morphologically, hypoxic neuronal death in cultures was accompanied by cell body swelling, a feature of necrosis, yet simultaneously exhibited some features of apoptosis such as TUNEL positivity and protection by cycloheximide. However, unlike in classical programmed cell death, adding buthionine sulfoximine, a potent inhibitor of glutathione synthesis, completely reversed the protective effect of cycloheximide. The results have demonstrated that free radical injury is the main mechanism of neuronal death in the present retinal culture, and suggest an intriguing possibility that free redical injury may become a prominent mechanism, when excitotoxic injury is masked.
