J Korean Ophthalmol Soc.  1997 Nov;38(11):1975-1986.

Mechanism of Hypoxia-Induced Cytotoxicity in Cultured Rat Retinal Neurons

• Yoon YH
• Lee J

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.

Keyword

Apoptosis; Cultured retinal neurons; Excitotoxicity; Free radical injury; Hypoxia-ischemia

MeSH Terms

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*
Buthionine Sulfoximine
Cycloheximide
Dizocilpine Maleate
Excitatory Amino Acid Antagonists
Glutathione
Retinaldehyde