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

作为一种基本方法，我们通过向前房内注射印度墨水来诱导大鼠的慢性高眼压。一周后，在不使用GONIO透镜的情况下，直接沿角膜缘对色素带进行直接激光光凝(PC)，并再次注射印度墨水，以维持高眼压在30 mm Hg以上7天。我们定期检测神经节细胞的凋亡变化，以及神经纤维层免疫染色的caspase-3。第3天开始出现凋亡的神经节细胞，第5天变得丰富。相反，神经纤维层表现出显著的caspase-3活性，从眼压升高后24小时开始，并持续到此后。我们阐明了caspase家族在急性青光眼模型大鼠青光眼神经节细胞死亡的执行过程中的作用。作为一种临床手段，激光散斑血流图(LSFG)是一种可以评估眼内微循环的非侵入性定量技术。本研究包括44例44眼原发性开角型青光眼(POAG)和44例44眼正常眼压性青光眼(NTG)。采用激光散射仪测量视神经头部血流速度平方模糊率。用线性回归分析SBR与Humphrey视野指数的相关性。正常对照组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，SBR和Humphrey视野指数之间没有明显的相关性。这些结果提示，在NTG组，视神经头循环的改变可能与视野损害有关，而在POAG组，与视野损害的关系可能较小。

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.