Apoptosis is induced by excitotoxicity in goldfish retina.

Abstract

Apoptosis is an important mechanism of cell death that occurs physiologically during development. Recently, it has been shown that the selective pattern of neuronal degeneration in some brain disorders or in excitotoxic animal models, can reveal signs of apoptosis. This work produces evidence that kainic acid, a non-NMDA receptor agonist, induces apoptotic cell death in the goldfish retina. DNA breaks are in situ detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). This reaction shows a large number of positive cells in the inner nuclear layer 48 hours after intravitreal kainic acid administration. TUNEL staining of apoptotic death was prevented by the non-NMDA glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) but not by the NMDA receptor antagonist MK-801 administration. Ultrastructural changes that occur in kainic acid affected retinal neurons (hypercondensation and clumping of the chromatin and shrinkage of the cytoplasm) are consistent with those described in programmed cell death. Our results indicate that the excitotoxicity of intravitreally injected kainic acid causes the degeneration of those neurons in the goldfish retina, that underwent apoptotic death.