Moon Jung-Il, Kim In-Beom, Gwon Jae-Sung, Park Myoung-Hee, Kang Tae-Hoon, Lim Eun-Jin, Choi Kyu-Ryong, Chun Myung-Hoon
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.
Cell Tissue Res. 2005 Apr;320(1):51-9. doi: 10.1007/s00441-004-1062-8. Epub 2005 Feb 16.
DBA/2J (D2) mice develop a form of progressive pigmentary glaucoma with increasing age. We have compared retinal cell populations of D2 mice with those in control C57BL/6J mice to provide information on retinal histopathology in the D2 mouse. The D2 mouse retina is characterized by a reduction in retinal thickness caused mainly by a thinning of the inner retinal layers. Immunocytochemical staining for specific inner retinal neuronal markers, viz., calbindin for horizontal cells; protein kinase C (PKC) and recoverin for bipolar cells, glycine, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and nitric oxide synthase (NOS) for amacrine cells, and osteopontin (OPN) for ganglion cells, was performed to detect preferentially affected neurons in the D2 mouse retina. Calbindin, PKC, and recoverin immunoreactivities were not significantly altered. Amacrine cells immunoreactive for GABA, ChAT, and OPN were markedly decreased in number, whereas NOS-immunoreactive amacrine cells increased in number. However, no changes were observed in the population of glycine-immunoreactive amacrine cells. These findings indicate a significant loss of retinal ganglion and some amacrine cells, whereas glycinergic amacrine cells, horizontal, and bipolar cells are almost unaffected in the D2 mouse. The reduction in amacrine cells appears to be attributable to a loss of GABAergic and particularly cholinergic amacrine cells. The increase in nitrergic neurons with the consequent increase in NOS and NO may be important in the changes in the retinal organization that lead to glaucomain D2 mice. Thus, the D2 mouse retina represents a useful model for studying the pathogenesis of glaucoma and mechanisms of retinal neuronal death and for evaluating neuroprotection strategies.
DBA/2J（D2）小鼠随着年龄增长会出现一种进行性色素性青光眼。我们将D2小鼠的视网膜细胞群体与对照C57BL/6J小鼠的进行了比较，以提供有关D2小鼠视网膜组织病理学的信息。D2小鼠视网膜的特征是视网膜厚度减小，主要是由于视网膜内层变薄。对特定的视网膜内层神经元标志物进行免疫细胞化学染色，即：用钙结合蛋白标记水平细胞；用蛋白激酶C（PKC）和恢复蛋白标记双极细胞，用甘氨酸、γ-氨基丁酸（GABA）、胆碱乙酰转移酶（ChAT）和一氧化氮合酶（NOS）标记无长突细胞，用骨桥蛋白（OPN）标记神经节细胞，以检测D2小鼠视网膜中优先受影响的神经元。钙结合蛋白、PKC和恢复蛋白的免疫反应性没有明显改变。对GABA、ChAT和OPN呈免疫反应性的无长突细胞数量明显减少，而对NOS呈免疫反应性的无长突细胞数量增加。然而，对甘氨酸呈免疫反应性的无长突细胞群体没有观察到变化。这些发现表明D2小鼠视网膜神经节细胞和一些无长突细胞显著丢失，而甘氨酸能无长突细胞、水平细胞和双极细胞几乎未受影响。无长突细胞的减少似乎归因于GABA能尤其是胆碱能无长突细胞的丢失。含氮能神经元的增加以及随之而来的NOS和NO的增加可能在导致D2小鼠青光眼的视网膜组织变化中起重要作用。因此，D2小鼠视网膜是研究青光眼发病机制、视网膜神经元死亡机制以及评估神经保护策略的有用模型。
