高浓度纤维蛋白原通过 ICAM-1 途径调节视网膜功能。

High Intraocular Concentration of Fibrinogen Regulates Retinal Function Via the ICAM-1 Pathway.

机构信息

Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan.

Department of Ophthalmology, Kansai Medical University, Hirakata, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):34. doi: 10.1167/iovs.65.13.34.

DOI:10.1167/iovs.65.13.34

PMID:39546292

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11578147/

Abstract

PURPOSE

Diabetic retinopathy (DR) is a significant complication of diabetes mellitus that can lead to progressive visual impairment. This study aimed to elucidate the role of fibrinogen, a protein whose serum and intraocular concentrations are elevated in patients with diabetes and DR, in the pathogenesis of DR.

METHODS

The changes in the protein levels of the neuronal marker tubulin-β3 (TUBB3) and retinal response induced by the intravitreal injections of 1× phosphate-buffered saline, 40 mg/mL of fibrinogen, and 40 mg/mL of fibrinogen in combination with anti-intracellular adhesion molecule-1 (ICAM-1) antibody in normal mice were observed using immunofluorescence, western blotting, and electroretinography.

RESULTS

High concentrations of fibrinogen led to a decrease in the expression of TUBB3 in immunofluorescence and western blotting. The amplitudes of the positive scotopic threshold response and b-wave were notably reduced after the injection of fibrinogen, indicating potential damage to the retinal ganglion cells. The co-administration of anti-ICAM-1 antibody effectively mitigated these fibrinogen-induced changes, indicating that fibrinogen-induced damage is mediated via the ICAM-1 pathway.

CONCLUSIONS

The present study underscores the significance of elevated intraocular fibrinogen levels as a pathogenic factor in DR. Involvement of the fibrinogen/ICAM-1 pathway presents new avenues for therapeutic intervention, especially in patients with treatment-resistant conditions.

摘要

目的

糖尿病视网膜病变（DR）是糖尿病的一种严重并发症，可导致进行性视力损害。本研究旨在阐明纤维蛋白原在 DR 发病机制中的作用，纤维蛋白原是一种在糖尿病和 DR 患者血清和眼内浓度升高的蛋白质。

方法

通过免疫荧光、western blot 和视网膜电图观察正常小鼠玻璃体内注射 1×磷酸盐缓冲液、40mg/ml 纤维蛋白原和 40mg/ml 纤维蛋白原与抗细胞间黏附分子-1（ICAM-1）抗体组合后，神经元标志物微管蛋白-β3（TUBB3）的蛋白水平变化和视网膜反应。

结果

高浓度纤维蛋白原导致免疫荧光和 western blot 中 TUBB3 的表达减少。纤维蛋白原注射后阳性暗适应阈值反应和 b 波的振幅明显降低，表明视网膜神经节细胞可能受损。抗 ICAM-1 抗体的联合给药有效缓解了这些纤维蛋白原引起的变化，表明纤维蛋白原诱导的损伤是通过 ICAM-1 途径介导的。