Wang Zhujian, Liu Yu, Zhou Min, Lei Boya, Chang Qing, Cao Wenjun
Department of Laboratory Medicine, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China.
Department of Ophthalmology, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China.
Front Cell Infect Microbiol. 2024 Dec 12;14:1502912. doi: 10.3389/fcimb.2024.1502912. eCollection 2024.
Acute retinal necrosis (ARN) caused by varicella-zoster virus (VZV) is associated with changes in specific proteins in the eye's fluid, particularly matrix metalloproteinase-3 (MMP-3), an enzyme that breaks down tissue structures, and tissue inhibitor of metalloproteinase-1 (TIMP-1), which regulates MMP activity. This study aims to investigate how these proteins correlate with the progression of ARN.
We analyzed aqueous humor samples from 33 patients with ARN and 23 control patients with virus-negative uveitis. MMP-3 levels were measured using immunoturbidimetry, and TIMP-1 levels were determined using an enzyme-linked immunosorbent assay. We examined the relationships between these protein levels and clinical findings using statistical correlation methods.
MMP-3, TIMP-1 were significantly higher in the aqueous humor of ARN patients compared to the controls (P<0.0001). Correlation analysis revealed a significant correlation between MMP-3 levels and TIMP-1 (r = 0.460, P = 0.007). The upregulation of MMP-3 and TIMP-1 was found to parallel VZV DNA load and IL-6 levels. Additionally, they exhibited negative correlation with best corrected visual acuity (BCVA) and positive correlation with the percentage of active retinal necrosis area.MMP-3 was markedly enhanced in all 14 cases of retinal detachment (RD), whereas TIMP-1 levels were significantly reduced in the same cohort of eyes. Patients with initial higher TIMP-1 levels have a significantly increased risk of developing RD, with a hazard ratio (HR) of 3.152 (95% CI, 1.082-9.18).
The imbalance between MMP-3 and TIMP-1 may play a critical role in the development and severity of ARN. Measuring these proteins in the eye's aqueous humor could be valuable for assessing disease progression and guiding treatment strategies, potentially improving outcomes for patients with virus-induced retinal diseases.
水痘-带状疱疹病毒（VZV）引起的急性视网膜坏死（ARN）与眼内液中特定蛋白质的变化有关，特别是基质金属蛋白酶-3（MMP-3），一种分解组织结构的酶，以及金属蛋白酶组织抑制剂-1（TIMP-1），它调节MMP的活性。本研究旨在探讨这些蛋白质与ARN进展的相关性。
我们分析了33例ARN患者和23例病毒阴性葡萄膜炎对照患者的房水样本。使用免疫比浊法测量MMP-3水平，使用酶联免疫吸附测定法测定TIMP-1水平。我们使用统计相关方法检查了这些蛋白质水平与临床发现之间的关系。
与对照组相比，ARN患者房水中的MMP-3、TIMP-1显著更高（P<0.0001）。相关性分析显示MMP-3水平与TIMP-1之间存在显著相关性（r = 0.460，P = 0.007）。发现MMP-3和TIMP-1的上调与VZV DNA载量和IL-6水平平行。此外，它们与最佳矫正视力（BCVA）呈负相关，与活动性视网膜坏死面积百分比呈正相关。在所有14例视网膜脱离（RD）病例中，MMP-3明显增强，而在同一组眼中TIMP-1水平显著降低。初始TIMP-1水平较高的患者发生RD的风险显著增加，风险比（HR）为3.152（95%CI，1.082 - 9.18）。
MMP-3与TIMP-1之间的失衡可能在ARN的发生和严重程度中起关键作用。测量眼房水中的这些蛋白质对于评估疾病进展和指导治疗策略可能有价值，有可能改善病毒诱导的视网膜疾病患者的预后。
