Fischer A J, Seltner R L, Poon J, Stell W K
Department of Anatomy and Lion's Sight Center, Faculty of Medicine, University of Calgary, Alberta, Canada.
J Comp Neurol. 1998 Mar 30;393(1):1-15.
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.
先前的研究表明，向雏鸡眼睛注射单次大剂量的N-甲基-D-天冬氨酸（NMDA）或喹啉酸（QA）会破坏许多视网膜无长突细胞，并诱导眼球过度生长并伴有近视。本研究的目的是确定对NMDA或QA敏感的不同视网膜细胞群，特别是那些被认为参与调节眼球生长的细胞群。将2皮摩尔的NMDA或0.2微摩尔的QA单侧注射到7日龄雏鸡的眼睛中，并在1、3或7天后制备视网膜用于观察。通过免疫细胞化学鉴定视网膜神经元，并通过对冰冻切片进行3'-末端标记来鉴定含有断裂DNA的细胞。NMDA和QA破坏了许多无长突细胞，包括那些对血管活性肠肽、甲硫氨酸脑啡肽和胆碱乙酰转移酶有免疫反应的细胞，但它们对酪氨酸羟化酶免疫反应性细胞影响很小。受QA和NMDA共同影响的其他细胞包括那些对谷氨酸脱羧酶、γ-氨基丁酸、小白蛋白、5-羟色胺和氨基羟基甲基异恶唑丙酸（AMPA）受体亚基GluR1和GluR2/3有免疫反应的细胞。基本不受QA或NMDA影响的细胞包括对蛋白激酶C（α和β亚型）有免疫反应的双极细胞和对胰高血糖素有免疫反应的无长突细胞。在暴露于QA或NMDA后1天，在许多无长突细胞和一些双极细胞中最大程度地检测到DNA片段化。我们提出，QA和NMDA引起的兴奋性毒性诱导特定无长突细胞群发生凋亡，并且这些作用是其他地方报道的QA和NMDA对眼球生长特异性影响的原因。
