Elucidation for pathogenic mechanism of glaucomatous optic neuropathy and retinal ganglion cell death

作为一种基本的方法，我们通过将印度墨水注入前房来诱导大鼠的眼内压慢性升高。一周后，我们直接沿着角膜利姆布斯进行直接激光光凝（PC），而不使用房角透镜，并再次注射印度墨水，以维持眼压在30 mmHg以上，持续7天。我们定期检查神经节细胞的凋亡变化，以及免疫染色的caspase-3在神经纤维层。第3天开始出现神经节细胞凋亡，第5天神经节细胞数量增多。相反，神经纤维层显示出在IOP升高后24小时开始的caspase-3的显著活化，并且此后持续。本研究阐明了caspase家族参与了大鼠急性青光眼模型眼内神经节细胞死亡的执行过程。激光散斑血流图（Laser speckle flowgraphy，LSFG）是一种无创、定量的眼内微循环检测技术，可作为临床应用的一种手段。本研究包括44例原发性开角型青光眼（POAG）和44例正常眼压性青光眼（NTG）患者的44只眼。用LSFG法测量视乳头血流速度的平方模糊率（SBR）。用线性回归分析评价SBR与Humphrey视野指数之间的相关性。NTG组的SBR与Humphrey视野指数呈正相关（r=0.299-0.354，p=0.019-0.049）。然而，在POAG组中未观察到SBR和Humphrey视野指数之间的显著相关性。提示NTG组视神经乳头循环改变与视野损害有关，POAG组视神经乳头循环改变与视野损害关系不大。

As a basic approachWe induced chronically elevated intraocular pressure in rats by injecting India ink into the anterior chamber. One week later, we performed direct laser photocoagulation (PC) of the pigmented band along the corneal limbus directly without using a gonio lens, and injected India ink again to sustain elevated IOP at above 30mmHg for 7 days. We periodically examined the apoptotic changes in the ganglion cells, as well as immunostained caspase-3 in the nerve fiber layer. Apoptotic ganglion cells began to appear on the 3rd day, and became abundant by the 5th day. In contrast, the nerve fiber layer showed a remarkable activation of caspase-3 beginning at 24 hours after IOP elevation and continued thereafter. We clarified the involvement of caspase family in the executive process of the glaucomatous ganglion cell death of the rat acute glaucoma model.As a clinical approachLaser speckle flowgraphy (LSFG) is a non-invasive and quantitative technique that can evaluate intraocular microcirculation. This study included 44 eyes of 44 patients with primary open-angle glaucoma (POAG) and 44 eyes of 44 patients with normal-tension glaucoma (NTG). To evaluate blood flow velocity of optic nerve head, the square blur rate (SBR) was measured by means of LSFG. The correlation between SBR and Humphrey visual field indices was evaluated with linear regression analysis. In the NTG group, SBR was positively correlated with Humphrey visual field indices (r=0.299-0.354, p=0.019-0.049). However, no significant correlation between SBR and Humphrey visual field indices was observed in the POAG group. These results suggested that the change in the circulation of the optic nerve head may be related to visual field damage in the NTG group but may be less involved in visual field damage in the POAG group.