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

作为一种基本方法，我们通过在大鼠前房注射墨汁来诱导长期升高的眼压。一周后，我们在不使用晶状体的情况下直接对角膜缘色素带进行直接激光光凝（PC），并再次注射墨汁，使IOP维持在30mmHg以上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天凋亡细胞增多。相比之下，神经纤维层显示caspase-3在IOP升高后24小时开始并持续激活。阐明caspase家族参与了大鼠急性青光眼模型青光眼神经节细胞死亡的执行过程。激光散斑血流成像（LSFG）是一种评估眼内微循环的无创定量技术。本研究纳入44例原发性开角型青光眼（POAG）的44只眼和44例正常张力型青光眼（NTG）的44只眼。采用LSFG测量视神经头血流速度的平方模糊率（SBR）。采用线性回归分析评价SBR与Humphrey视野指数的相关性。NTG组SBR与Humphrey视野指数呈正相关（r=0.299 ~ 0.354, p=0.019 ~ 0.049）。而POAG组SBR与Humphrey视野指数无显著相关性。这些结果提示，视神经头循环的改变可能与NTG组的视野损害有关，而与POAG组的视野损害关系较小。

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.