Immunocytochemical characterization of quisqualic acid- 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 accompanied by myopia. The purpose of this study was to identify distinct populations of retinal cells, particularly those believed to be involved in regulating ocular growth, that are sensitive to NMDA or QA. Two pmol of NMDA or 0.2 micromol of QA were injected unilaterally into eyes of 7-day-old chicks, and retinas were prepared for observation 1, 3, or 7 days later. Retinal neurons were identified by using immunocytochemistry, and cells containing fragmented DNA were identified by 3'-nick-end labelling in frozen sections. NMDA and QA destroyed many amacrine cells, including those immunoreactive for vasoactive intestinal polypeptide, Met-enkephalin, and choline acetyltransferase, but they had little effect upon tyrosine hydroxylase-immunoreactive cells. Other cells affected by both QA and NMDA included those immunoreactive for glutamic acid decarboxylase, gamma-aminobutyric acid, parvalbumin, serotonin, and aminohydroxy methylisoxazole propionic acid (AMPA) receptor subunits GluR1 and GluR2/3. Cells largely unaffected by QA or NMDA included bipolar cells immunoreactive for protein kinase C (alpha and beta isoforms) and amacrine cells immunoreactive for glucagon. DNA fragmentation was detected maximally in many amacrine cells and in some bipolar cells 1 day after exposure to QA or NMDA. We propose that excitotoxicity caused by QA and NMDA induces apoptosis in specific populations of amacrine cells and that these actions are responsible for the ocular growth-specific effects of QA and NMDA reported elsewhere.
Fischer
A J
AJ
Department of Anatomy and Lion's Sight Center, Faculty of Medicine, University of Calgary, Alberta, Canada. ajfische@acs.ucalgary.ca
Seltner
R L
RL
Poon
J
J
Stell
W K
WK
D000818:Animals; D000918:Antibody Specificity; D015415:Biomarkers; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology; D002645:Chickens / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000276:immunology; D004298:Dopamine / Q000502:physiology; D004744:Enkephalin, Methionine / Q000032:analysis / Q000276:immunology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D005934:Glucagon / Q000032:analysis / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000276:immunology; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000737:chemistry; D007527:Isoenzymes / Q000032:analysis / Q000276:immunology; D008247:Lysosomes / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D026901:Membrane Transport Proteins; D009216:Myopia / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D027361:Organic Anion Transporters; D010320:Parvalbumins / Q000032:analysis / Q000276:immunology; D011493:Protein Kinase C / Q000032:analysis / Q000276:immunology; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D016318:Quisqualic Acid / Q000494:pharmacology; D018091:Receptors, AMPA / Q000032:analysis* / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis* / Q000276:immunology; D012160:Retina / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology*; D012701:Serotonin / Q000032:analysis / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000276:immunology; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000276:immunology
D015415:Biomarkers; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D050485:GABA Plasma Membrane Transport Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009498:Neurotoxins; D027361:Organic Anion Transporters; D010320:Parvalbumins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D005934:Glucagon; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D005968:Glutamate Decarboxylase; D004298:Dopamine