IMMUNOCYTOCHEMICAL CHARACTERIZATION OF QUISQUALIC ACID-INDUCED AND N-METHYL-D-ASPARTATE-INDUCED EXCITOTOXICITY IN THE RETINA OF CHICKS

A single, large dose of N-methyl-D-aspartate (NMDA) or quisqualic acid (QA) injected into the chick eye has been shown previously to destroy many retinal amacrine cells and to induce excessive ocular growth acc ompanied by myopia. The purpose of this study was to identify distinct populations of retinal cells, particularly those believed to be invol ved in regulating ocular growth, that are sensitive to NMDA or QA. Two mu mol of NMDA or 0.2 mu mol of QA were injected unilaterally into ey es of 7-day-old chicks, and retinas were prepared for observation 1, 3 , or 7 days later. Retinal neurons were identified by using immunocyto chemistry, and cells containing fragmented DNA were identified by 3'-n ick-end labelling in frozen sections. NMDA and QA destroyed many amacr ine cells, including those immunoreactive for vasoactive intestinal po lypeptide, Met-enkephalin, and choline acetyltransferase, but they had little effect upon tyrosine hydroxylase-immunoreactive cells. Other c ells affected by both QA and NMDA included those immunoreactive for gl utamic acid decarboxylase, gamma-aminobutyric acid, parvalbumin, serot onin, and aminohydroxy methylisoxazole propionic acid (AMPA) receptor subunits GluR1 and GluR2/3. Cells largely unaffected by QA or NMDA inc luded bipolar cells immunoreactive for protein kinase C (alpha and bet a isoforms) and amacrine cells immunoreactive for glucagon. DNA fragme ntation was detected maximally in many amacrine cells and in some bipo lar cells 1 day after exposure to QA or NMDA. We propose that excitoto xicity caused by QA and NMDA induces apoptosis in specific populations of amacrine cells and that these actions are responsible for the ocul ar growth-specific effects of QA and NMDA reported elsewhere. J. Comp. Neurol. 393:1-15, 1998. (C) 1998 Wiley-Liss, Inc.