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

作为基本方法，我们通过将印度墨水注入前房来诱导大鼠眼内压慢性升高。一周后，我们在不使用房角镜片的情况下，直接沿角膜缘色素带进行直接激光光凝（PC），并再次注射印度墨水，将眼压维持在30mmHg以上，持续7天。我们定期检查神经节细胞的凋亡变化以及神经纤维层中免疫染色的 caspase-3。凋亡的神经节细胞在第3天开始出现，并在第5天变得丰富。相比之下，神经纤维层显示 caspase-3 在 IOP 升高后 24 小时开始显着激活，并持续此后。我们阐明了caspase家族参与大鼠急性青光眼模型青光眼神经节细胞死亡的执行过程。作为一种临床方法，激光散斑血流成像（LSFG）是一种可评估眼内微循环的非侵入性定量技术。这项研究包括 44 名原发性开角型青光眼 (POAG) 患者的 44 只眼睛和 44 名正常眼压性青光眼 (NTG) 患者的 44 只眼睛。为了评估视神经乳头的血流速度，采用LSFG测量平方模糊率(SBR)。通过线性回归分析评估 SBR 和 Humphrey 视野指数之间的相关性。 NTG组中，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 视野指数之间存在显着相关性。这些结果表明，NTG组视神经乳头循环的变化可能与视野损伤有关，但POAG组视神经乳头循环的变化可能与视野损伤关系较小。

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.