EFEMP1-Mediated Regulation of Choroidal Vascular Dysfunction in Myopia: Insights Into the FOXO3/VEGFA Pathway as a Therapeutic Target

Purpose: This study investigates the role of EFEMP1 in choroidal vascular dysfunction and its implications for myopia progression, specifically focusing on the FOXO3/VEGFA signaling pathway as a potential therapeutic target. Methods: We utilized adeno-associated virus (AAV) to overexpress and knock down EFEMP1 in the choroid of guinea pigs. Subsequent proteomic analyses were conducted on the choroidal tissue. We used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify relevant pathways and genes. In vitro experiments were performed on RF/6A cells, where both EFEMP1 and FOXO3 underwent overexpression and knockdown. We conducted a series of cell culture experiments, including assessments of cell proliferation, migration, tube formation, and choroidal sprouting assays, to evaluate the functional effects of EFEMP1. Quantitative reverse transcription PCR and Western blot analyses were utilized to measure gene and protein expression levels. Results: Silencing EFEMP1 significantly reduced choroidal vascular dysfunction and slowed the progression of myopia. Proteomic analysis demonstrated that EFEMP1 regulates FOXO3 activity, resulting in increased VEGFA expression in RF/6A cells and promoting angiogenesis. Conversely, knockdown of FOXO3 led to decreased VEGFA levels, confirming that EFEMP1 modulates VEGFA expression through FOXO3. Conclusions: Targeting EFEMP1 may offer a novel therapeutic strategy for the prevention and treatment of myopia by alleviating associated vascular dysregulation. Further exploration of the FOXO3/VEGFA pathway could provide additional insights into therapeutic interventions for myopia.