RESUMO
Objective: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on the expression levels of transforming growth factor-beta (TGF-ß) and its related microRNAs in the vitreous of patients with proliferative diabetic retinopathy (PDR). Methods: This cross-sectional study included 67 patients (67 eyes), 38 males and 29 females, aged (54.37±11.70) years, who underwent vitrectomy from June 2020 to February 2021. There were 45 PDR patients (45 eyes), including 29 patients (29 eyes) without anti-VEGF therapy in the disease group and 16 patients (16 eyes) who were admitted at 7 days after anti-VEGF therapy in the treatment group. The other 22 idiopathic macular hole patients (22 eyes) were in the negative control group. The microRNA (hsa-miR-24-3p and hsa-miR-197-3p) levels in the vitreous of 36 patients (12 cases randomly chosen from each group) were detected by quantitative reverse transcription polymerase chain reaction. The levels of TGF-ß and VEGF-A in the vitreous of 67 patients were detected by enzyme-linked immunosorbent assay. Target gene prediction of hsa-miR-24-3p and hsa-miR-197-3p was performed on RNAhybrid, miRanda and TargetScan7.2 databases, and pathway enrichment analyses were conducted for all target mRNAs. One-way ANOVA was used to compare the levels of growth factors and microRNAs among the three groups, and the least significant difference method was used for multiple comparisons between groups. Pearson correlation test was used to analyze the correlation between growth factors and microRNAs. Results: The expression levels of VEGF-A, TGF-ß, hsa-miR-24-3p and hsa-miR-197-3p were (158.15±17.72) pg/ml, (640.47±24.80) pg/ml, 0.81±0.11 and 1.07±0.15 in the control group, (1 047.54±26.61) pg/ml, (3 553.17±92.61) pg/ml, 8.50±2.33 and 12.23±3.38 in the disease group, and (778.10±27.73) pg/ml, (3 376.02±78.83) pg/ml, 4.54±0.67 and 3.90±0.65 in the treatment group, respectively. All indicators were significantly higher in the disease group than those in the control group (F=355.581, 440.538, 7.546 and 7.546; all P<0.05). The expression levels of VEGF-A, hsa-miR-24-3p and hsa-miR-197-3p in the treatment group were significantly lower than those in the disease group (all P<0.05). The concentration of TGF-ß was not statistically significantly lower in the treatment group compared to the disease group. The concentrations of VEGF-A and TGF-ß were significantly positively correlated with the expression levels of hsa-miR-24-3p and hsa-miR-197-3p in the vitreous of randomly chosen 36 patients (r=0.48, 0.51, 0.40 and 0.42; all P<0.05). Pathway enrichment analysis showed that some target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p were involved in VEGF and TGF-ß signal pathways. Conclusions: In the vitreous of patients with PDR, hsa-miR-24-3p and hsa-miR-197-3p were positively related to VEGF-A and TGF-ß, and may be potential risk factors. Anti-VEGF treatment can significantly reduce the expression level of TGF-ß-related microRNAs, namely hsa-miR-24-3p and hsa-miR-197-3p, but cannot effectively reduce the concentration of TGF-ß, suggesting that combined anti-TGF treatment may be beneficial for delaying the progression of PDR. Furthermore, it may be a new research direction of PDR to validate the target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p involved in VEGF and TGF-ß signal pathways. (Chin J Ophthalmol, 2021, 57: 922-929).
