Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo 113-8655, Japan.
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Int J Mol Sci. 2020 Feb 17;21(4):1339. doi: 10.3390/ijms21041339.
We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina-brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.
我们研究了外侧膝状体核（LGN）在实验性高眼压（OH）雪貂模型中的结构变化和星形胶质细胞反应。在 10 只雪貂中，通过将培养的结膜细胞注射到右眼前房来诱导 OH；6 只正常雪貂作为对照。用霍乱毒素 B 进行顺行轴突追踪显示，接受 OH 眼投射的 LGN 层有明显的萎缩性损伤。用针对神经元核抗原（NeuN）、胶质纤维酸性蛋白（GFAP）和 Iba-1 的抗体进行免疫组织化学分析，以特异性标记 LGN 中的神经元、星形胶质细胞和小胶质细胞。在接受 OH 眼投射的 LGN 层中，观察到 NeuN 免疫反应性显著降低，GFAP 和 Iba-1 免疫反应性增加。有趣的是，免疫反应性的变化在 LGN 层之间存在显著差异。C 层比 A 和 A1 层显示出更严重的损伤。还观察到 LGN 的继发性退行性变化，包括每个 LGN 层中的神经元损伤和星形胶质细胞反应。这些结果表明，我们的 OH 雪貂模型对于研究青光眼视觉通路中视网膜-脑传递过程中的损伤是有价值的。首次揭示了 C 层的易损性。
