Metabolomic and transcriptomic analysis reveals metabolic-immune interactions in choroid neovascularization.

Abstract

Choroid neovascularization (CNV) is a distinct type of age-related macular degeneration (AMD) with a poor prognosis and responsible for the majority of vision loss in the elderly population. The laser-induced CNV model is a well-established animal model frequently used to study CNV. In this study, we performed an integrated analysis of metabolomic and transcriptomic data from CNV samples, utilizing multiple approaches including single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and weighted gene co-expression network analysis (WGCNA), alongside various bioinformatics platforms, to identify key metabolic and immune signatures and to investigate their interplay during angiogenesis. Dominant infiltration of macrophages and monocytes was detected and a positive correlation between dysregulated riboflavin metabolism and angiogenesis pathways was characterized. Hub genes such as ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) and acid phosphatase 5, tartrate resistant (ACP5) emerged as potential central regulators of immune-metabolic crosstalk in CNV. The classification of the immune and metabolic landscape and their critical interactions in CNV models will enhance the understanding of the pathogenesis of neovascular AMD and other neovascular eye diseases, contributing to the development of multi-targeted therapeutic strategies with better efficacy.