Quinolinate. A selective neurotoxin in embryonic and posthatching chicken retinas

Quinolinate (QUIN), an endogenous dicarboxylic amino acid, structurally related to the putative retinal neurotransmitter aspartate, acts as a specific neurotoxin in the chick neural retina. Qualitative analysis of QUIN's neurotoxic effects reveals that sensitivity to the amino acid is first detected in the 9-day-old embryonic chick retina. Nuclei and cytoplasm of some cells in the inner region of the inner nuclear layer and in the ganglion cell layer appear hypochromatic or electron lucent when examined by light or electron microscopy, respectively. Between day 10 and 12, the sensitivity of the embryonic retina to QUIN increases and remains around the day 12 level throughout the remaining embryonic and initial posthatching period. Cells in the inner half of the inner nuclear layer continue to be the most severely affected throughout retinal development, ganglion cells less so. Photoreceptor and most cells in the outer region of the inner nuclear layer remain undamaged. QUIN effects are partially reversible: retinas exposed to QUIN briefly in vitro and then transferred to fresh QUIN-free medium are not as severely affected as those allowed no recovery time. In day 1 posthatching chick retinas, similar patterns of QUIN-toxicity were observed in vitro (0.5-5 mM QUIN; 5-30 min) and in vivo (200-600 micrograms QUIN/eye; 0.5-24 hr following intravitreal injection).