MMP-3 and TIMP-1 as prognostic biomarkers in VZV-induced retinal necrosis

Zhujian Wang; Yu Liu; Min Zhou; Boya Lei; Qing Chang; Wenjun Cao

doi:10.3389/fcimb.2024.1502912

MMP-3 and TIMP-1 as prognostic biomarkers in VZV-induced retinal necrosis

Front Cell Infect Microbiol. 2024 Dec 12:14:1502912. doi: 10.3389/fcimb.2024.1502912. eCollection 2024.

Authors

Zhujian Wang¹, Yu Liu¹, Min Zhou², Boya Lei², Qing Chang², Wenjun Cao¹

Affiliations

¹ Department of Laboratory Medicine, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China.
² Department of Ophthalmology, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: acute retinal necrosis; aqueous humor; metalloproteinase-3; tissue inhibitors of metalloproteinase-1; varicella-zoster virus.

MeSH terms

Adult
Aged
Aqueous Humor* / metabolism
Aqueous Humor* / virology
Biomarkers* / analysis
Biomarkers* / metabolism
DNA, Viral
Female
Herpesvirus 3, Human* / isolation & purification
Humans
Interleukin-6 / analysis
Interleukin-6 / metabolism
Male
Matrix Metalloproteinase 3* / metabolism
Middle Aged
Prognosis
Retinal Necrosis Syndrome, Acute* / diagnosis
Retinal Necrosis Syndrome, Acute* / virology
Tissue Inhibitor of Metalloproteinase-1* / metabolism
Varicella Zoster Virus Infection / complications
Viral Load
Young Adult

Substances

Matrix Metalloproteinase 3
Tissue Inhibitor of Metalloproteinase-1
Biomarkers
MMP3 protein, human
TIMP1 protein, human
Interleukin-6
DNA, Viral

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (Grant no. 81770944 and 81700862) and Science Foundation of Ministry of Education (Grant no. 2023JQ006).