MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular...

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• Genetic studies link the matrix metalloproteinase-9 (MMP9) gene to neovascular age-related macular degeneration (nvAMD) risk.
• However, genotype-phenotype associations between MMP9 and nvAMD remain unclear.

Purpose of the Study:

• To investigate how MMP9 genotype and T-cell subsets affect structural and functional outcomes in nvAMD patients.
• To explore the role of MMP9 in the immunopathogenesis of nvAMD.

Main Methods:

• Reanalyzed single-cell RNA sequencing data and used ELISA/flow cytometry to measure MMP9 expression in human choroids.
• Genotyped the nvAMD risk SNP (rs4810482) in 38 nvAMD patients and quantified retinal fluid using OCT image analysis.
• Performed high-dimensional immunophenotyping on a subset of nine patients.

Main Results:

• MMP9 expression was predominant in mature THP-1-derived dendritic-like cells.
• Patients with the TC genotype of MMP9 showed greater disease severity and higher retinal fluid volume compared to CC or TT genotypes.
• Increased circulating CD8+ effector memory T cells re-expressing CD45RA (TEMRA) correlated with residual subretinal fluid, indicating persistent disease activity.

Conclusions:

• MMP9 genotype significantly impacts structural and functional outcomes in nvAMD.
• Systemic immune dysregulation and a MMP9-dendritic-T-cell axis are implicated in nvAMD immunopathogenesis.
• This axis represents a potential therapeutic target for nvAMD.