Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado, United States.
Asociación Para Evitar La Ceguera, Mexico City, Mexico.
Invest Ophthalmol Vis Sci. 2020 Sep 1;61(11):39. doi: 10.1167/iovs.61.11.39.
A growing body of evidence points to complement dysregulation in diabetes. Early studies have indicated the presence of complement components inside the eye in patients with diabetic retinopathy, but these data have been confounded by leakage of proteins from the systemic circulation into the vitreous cavity.
We took samples of plasma and vitreous from patients with and without proliferative diabetic retinopathy (PDR) and measured levels of 16 complement components as well as albumin. We employed a normalized ratio using local and systemic complement and albumin levels to control for vascular leakage into the vitreous cavity.
Before normalizing, we found significantly higher levels of 16 complement components we measured in PDR eyes compared to controls. After normalizing, levels of C4, factor B, and C5 were decreased compared to controls, while C3a and Ba levels were elevated compared to controls. We also found higher ratios of C3a/C3, C5a/C5, and Ba/factor B in PDR eyes compared to controls.
We found evidence of local, intraocular activation of C3, C5, and factor B. The normalized data suggest involvement of the alternative complement pathway. By showing activation of specific complement components in PDR, this study identifies targets for diagnostic and therapeutic potential.
越来越多的证据表明补体失调与糖尿病有关。早期研究表明,糖尿病性视网膜病变患者的眼睛内存在补体成分,但这些数据受到来自全身循环的蛋白质漏入玻璃体腔的干扰。
我们从患有和不患有增生性糖尿病性视网膜病变(PDR)的患者中采集血浆和玻璃体样本,并测量 16 种补体成分以及白蛋白的水平。我们采用了一种使用局部和全身补体及白蛋白水平的归一化比值来控制玻璃体腔的血管渗漏。
在归一化之前,我们发现 PDR 眼中我们测量的 16 种补体成分的水平明显高于对照组。归一化后,与对照组相比,C4、因子 B 和 C5 的水平降低,而 C3a 和 Ba 的水平升高。与对照组相比,我们还发现 PDR 眼中 C3a/C3、C5a/C5 和 Ba/因子 B 的比值更高。
我们发现 C3、C5 和因子 B 的局部、眼内激活的证据。归一化数据提示替代补体途径的参与。通过显示 PDR 中特定补体成分的激活,本研究确定了诊断和治疗潜力的靶标。