Effect of Endogenous FGF21 Deficiency on the Inflammatory Microenvironment of the Retina

BACKGROUND: While the systemic metabolic role of fibroblast growth factor 21 (FGF21) is well-established, its function in retinal homeostasis and its link to retinal diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) remains poorly understood. This study investigated the impact of endogenous FGF21 deficiency on the retinal immune microenvironment. METHODS: Retinal structure was assessed in FGF21 KO and wild-type mice using spectral-domain optical coherence tomography. Transcriptomic profiles of the retina/choroid were analyzed by RNA-seq. Differentially expressed genes (DEGs) were identified (DESeq2, FDR <0.05), clustered, and interrogated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Immune-cell composition was inferred with ImmuCellAI. RESULTS: < 0.01) without change in total macrophage number. Expression of key inflammatory mediators including Il1b was concordantly altered. CONCLUSIONS: This work establishes endogenous FGF21 as a crucial local immunomodulator and defines a novel mechanistic link to retinal disease susceptibility, supporting its further exploration as a therapeutic target.