University Eye Clinic Maastricht, Maastricht Medical Center, Maastricht, the Netherlands; Research School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
University Eye Clinic Maastricht, Maastricht Medical Center, Maastricht, the Netherlands.
Exp Eye Res. 2021 Mar;204:108460. doi: 10.1016/j.exer.2021.108460. Epub 2021 Jan 23.
We recently performed a combined analysis of publicly available proteomic studies of aqueous humor (AH) of patients with primary open angle glaucoma (POAG). This analysis revealed changes in complement protein concentrations in the AH of progressive POAG patients, which suggested that the complement system may play a role in POAG progression. As the proteomic studies could not provide information on the activity of the complement system, we addressed this question in the current study.
Blood serum and AH were obtained from 30 patients: 10 progressive POAG, 10 stable POAG and, as controls, 10 cataract patients. Glaucoma patients with a visual field Mean Deviation (MD) change of at least 1.0 dB/year were considered progressive; a MD change of less than 0.5 dB/year was considered stable. The ratio between the levels of complement factors C3a and C3 was used as indicator for activation of the complement cascade. The factors were measured with commercially available ELISA kits.
AH levels of complement factors C3 and C3a did not significantly differ between groups. In serum, complement factor C3 did not differ between groups whereas C3a was significantly elevated in progressive POAG patients compared to controls (p < 0.05). The resulting complement C3a/C3 ratio was significantly higher in progressive POAG patients in both AH (p < 0.05) and serum (p < 0.01), and this ratio significantly correlated between the two body fluids (p < 0.001). Furthermore, there was a strong correlation between disease progression and C3a/C3 activation ratio both in AH (p < 0.01) and in serum (p < 0.001). The higher the complement C3a/C3 ratio, the faster the disease progression.
Significant increases in AH and serum complement C3a/C3 ratios were observed in progressive POAG patients but not in stable POAG patients. Furthermore, the complement C3a/C3 ratio correlated strongly with the rate of disease progression in both AH and serum. These findings suggest that activation of the complement system plays a role in glaucoma progression and that progressive glaucoma patients may have systemic changes in complement activation.
我们最近对原发性开角型青光眼（POAG）患者房水的公开蛋白质组学研究进行了综合分析。该分析揭示了进行性 POAG 患者房水中补体蛋白浓度的变化，这表明补体系统可能在 POAG 进展中发挥作用。由于蛋白质组学研究无法提供补体系统活性的信息，我们在当前研究中解决了这个问题。
从 30 名患者中获得血清和房水：10 名进行性 POAG、10 名稳定型 POAG 和 10 名白内障患者作为对照。视野平均偏差（MD）变化至少 1.0 dB/年的青光眼患者被认为是进行性的；MD 变化小于 0.5 dB/年的被认为是稳定的。补体因子 C3a 和 C3 的水平之比被用作补体级联激活的指标。使用市售的 ELISA 试剂盒测量这些因子。
各组之间房水中补体因子 C3 和 C3a 的水平没有显著差异。在血清中，各组之间补体因子 C3 没有差异，而 C3a 在进行性 POAG 患者中明显高于对照组（p<0.05）。在进行性 POAG 患者的房水（p<0.05）和血清（p<0.01）中，补体 C3a/C3 比值显著升高，并且两种体液之间存在显著相关性（p<0.001）。此外，在房水（p<0.01）和血清（p<0.001）中，疾病进展与 C3a/C3 激活比值之间存在很强的相关性。补体 C3a/C3 比值越高，疾病进展越快。
在进行性 POAG 患者中观察到房水和血清补体 C3a/C3 比值显著增加，但在稳定型 POAG 患者中未观察到。此外，补体 C3a/C3 比值与房水和血清中的疾病进展率密切相关。这些发现表明补体系统的激活在青光眼进展中起作用，并且进行性青光眼患者可能在补体激活方面存在全身性变化。
