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Updated: Apr 30, 2026
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Effect of Endogenous FGF21 Deficiency on the Inflammatory Microenvironment of the Retina
Ting-Ting Zhao1,2, Ming-Kai Chang3, Bai-Yun Shen2
1Department of Ophthalmology, Aier Eye Hospital, Jinan University, 510071 Guangzhou, Guangdong, China.
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:
FGF21 KO mice showed no overt retinal structural defects under baseline conditions. Nevertheless, 449 DEGs were identified (293 up, 156 down in knockout). Pathway analysis revealed significant enrichment of cytokine-cytokine receptor interaction, chemokine signaling, and Jak-STAT cascades. Immune deconvolution indicated a significant increase in M2-polarised macrophages (p < 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.
