A quantitative analysis of the effects of excitatory neurotoxins on retinal ganglion cells in the chick.

The present study examines the differential effects of three excitotoxins, kainic acid (KA), N-methyl-D-aspartate (NMDA), and alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) on neurons within the ganglion cell layer (GCL) of the chick retina. Two-day-old chicks were given a single, 5 microliters, intravitreal injection of KA, NMDA, or AMPA at a range of doses. Following treatment with 40 nmol KA, there was a 21% loss of neurons in the GCL. At 200 nmol KA, the loss increased to 46%. Exposure to KA eliminated mainly small neurons of soma area 5-15 microns2, and medium-sized ganglion cells of soma area 15-25 microns2. Large ganglion cells (greater than 25 microns2) remained unaffected. The vast majority of small cells were probably displaced amacrine cells. Exposure to 400 nmol NMDA resulted in a 14% loss of neurons, predominantly involving the large ganglion cells. At a dose of 3000 nmol NMDA, no further loss of cells was evident. Exposure to 200 nmol AMPA resulted in a 30% loss of large and some medium-sized ganglion cells. In a further series of experiments, exposure to excitotoxin was followed by a retinal scratch, which eliminated retinal ganglion cells within the axotomized region. The results indicate that only a small proportion of displaced amacrine cells are destroyed by NMDA and AMPA, whereas virtually all displaced amacrine cells are sensitive to KA. The findings of this study indicate the existence of subclasses of ganglion cells with specificity towards different types of excitatory amino acids (EAA).