Conclusion
We provide new evidence that asthma could be a risk factor for CNV development via the TGF-β1/Smad signalling pathway. A TGF-β inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.
Methods
Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-β1, TGF-β2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group.
Results
In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-β1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-β inhibitor, a distinct decline in VEGF, TGF-β1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased.