Brain Research Institute, University of Zürich, and Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Invest Ophthalmol Vis Sci. 2014 Jun 26;55(7):4476-89. doi: 10.1167/iovs.14-14521.
Ischemic insults give rise to severe visual deficits after blood vessel occlusion. In this study we investigated the effects of retinal stroke on the direction-selective circuit of the inner retina in a new adult mouse model.
The inner retinal blood flow was interrupted for 60 minutes by ligating the ophthalmic arteries and veins in the optic nerve sheath. The optokinetic response (OKR) was measured to assess ischemia/reperfusion-mediated functional deficits and structural changes were studied by immunohistochemistry.
Ischemia/reperfusion induced reactive gliosis and degeneration of the inner retina. The OKR was almost completely abolished from 7 days after reperfusion, whereas approximately 40% of retinal ganglion cells were still alive. Ischemia led to severe degeneration of the processes of starburst amacrine cells (SAC), which cell bodies are in the ganglion cell layer (ON SACs), and to a lesser extent of the dendrites of SACs, which cell bodies are in the inner nuclear layer (OFF SACs). In addition, the elimination of retinal ganglion cells, direction-selective ganglion cells, and ON SACs was much greater at 10 days and 21 days than that of OFF SACs. After reperfusion, P-Stat3 was transiently activated in ganglion cells, whereas P-Erk1/2 signal was specifically detected in Müller glia.
These results show a pronounced destruction of the ON direction-selective circuit in the inner retina that correlated with the irreversible loss of the OKR early after ischemia/reperfusion.
血管阻塞后会引起缺血性损伤，导致严重的视觉缺陷。在这项研究中，我们在一种新的成年小鼠模型中研究了视网膜卒中对内视网膜方向选择性回路的影响。
通过结扎视神经鞘中的眼动脉和静脉，阻断内视网膜血流 60 分钟。通过视动反应（OKR）测量来评估缺血/再灌注介导的功能缺陷，并通过免疫组织化学研究结构变化。
缺血/再灌注引起反应性神经胶质增生和内视网膜变性。再灌注后 7 天，OKR 几乎完全消失，而大约 40%的视网膜神经节细胞仍然存活。缺血导致星爆型无长突细胞（SAC）的过程严重退化，这些细胞的体位于神经节细胞层（ON SACs），而 OFF SACs 的树突退化程度较轻。此外，10 天和 21 天时视网膜神经节细胞、方向选择性神经节细胞和 ON SACs 的消除程度明显大于 OFF SACs。再灌注后，P-Stat3 在神经节细胞中短暂激活，而 P-Erk1/2 信号则特异性地在 Müller 胶质细胞中检测到。
这些结果表明，ON 方向选择性回路在内视网膜中受到明显破坏，这与缺血/再灌注后早期 OKR 的不可逆丧失相关。
