Neurotoxic Effects of Kainic Acid on Developing Chick Retina

Abstract

The neurotoxic effects of kainic acid (KA) on developing neurons in the chick retina was investigated in an in vitro preparation. Eyecups from chick embryos at 6 (E-6), 8, 10, 12, 14, 16, and 20 days of incubation and from chicks on day 1 posthatch (D-1) were exposed to different doses of KA for 30 min and then processed for light microscopy. Neurotoxic damage was evaluated by the presence of swollen cell bodies, containing pale cytoplasm and pyknotic nuclei. At E-8, amacrine cells first became sensitive to KA and displayed neurotoxic damage at a threshold concentration of 20 µM. Their sensitivity to KA increased over the following 4 days, so that by E-12 they attained a threshold sensitivity of 5.0 µMKA. At E-14, one third of the retinae showed amacrine cell damage at 0.5–2.0 µM KA, less than the threshold dose of 5.0 µM KA required at D-1. Bipolar cells first become sensitive to KA at E-12, at a threshold concentration of 5.0 µM. The threshold concentration decreased over the following 10 days: 2.0 µM at E-16,1.0 µM at E-20, and 0.5 µM at D-1. At E-8 and E-10, horizontal cells were susceptible to a relatively high concentration of 80 µM KA. The sensitivity to KA is evident prior to the formation of photoreceptor input. These results indicate that amacrine and horizontal cells are susceptible to KA at an earlier age than bipolar cells. Both amacrine and bipolar cells exhibit an age-dependent relationship with the threshold concentration of KA required to cause neurotoxicity; in general, the older the embryo, the lower the dose of KA. However, the increased susceptibility of amacrine cells at E-14 suggests a transient hypersensitivity to KA during this period which may reflect an overproduction of the receptor-ionic channel complex necessary for KA to exert its effect.

Guanine nucleotides protect against kainate toxicity in an ex vivo chick retinal preparation

“…Thus retina differs from other chick brain regions, such as tectum and cerebellum, where only the low‐affinity site has been found [10, 25]. These receptors would be, in principle, the molecular substrate for the excitotoxic action of KA in the chick retina, already a firmly established fact [14–21, 26, 27]. The characteristic sigmoidal shape of the dose‐dependence curve for KA (Fig.…”

“…The need for a simple system to test the validity and the relative potency of different GN analogs and derivatives as neuroprotectors has prompted us to explore the suitability of the chick retina as a model to analyze the ability of GNs to antagonize the toxic actions of excitatory amino acids. Although early descriptions of the deleterious effects of glutamate on the mouse retina [13]were based on the parenteral administration of the amino acid (see [14]for a discussion), the use of the ex vivo chick (or mouse) retinal preparation for excitotoxicity analysis was later successfully adopted in several laboratories [15–21]. We have taken advantage of a further adaptation of this retinal model to set up a simple and sensitive system to evaluate the neuroprotective effects of GNs and other EAA antagonists on the acute and delayed effects of a single dose of kainate.…”

Selective reduction of oscillatory potentials and pattern electroretinograms after retinal ganglion cell damage by disease in humans or by kainic acid toxicity in cats

“…Previous studies also found initial effects on ganglion cell bodies, but at a threshold of 100 nmol [22]. Kainic acid neurotoxicity has been most extensively studied in the chicken retina [24][25][26][27][28]. There is a dose-dependent sensitivity, with off-center biopolar cells that are depolarized being most sensitive.…”

“…In several species, intravitreally injected kainic acid has been shown to be neurotoxic to specific neuronal populations [19][20][21][22][23][24][25][26][27][28]. In the cat, the ganglion cells have been said to be the first affected [22].…”