Effect of ranibizumab on diabetic retinopathy the vascular endothelial growth factor/STAT3/glial fibrillary acidic protein pathway.

BACKGROUND

Diabetic retinopathy (DR) is the leading cause of vision loss in patients with diabetes. The vascular endothelial growth factor (VEGF) pathway plays a critical role in the pathogenesis of DR, and ranibizumab, an anti-VEGF agent, has shown promise in its treatment. Signal transducer and activator of transcription 3 (STAT3) is involved in inflammatory processes and cellular signaling, while glial fibrillary acidic protein (GFAP) is a marker of glial cell activation, both contributing to retinal damage in DR. However, the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.

AIM

To investigate the role of ranibizumab in early DR the VEGF/STAT3/GFAP pathway.

METHODS

Adult retinal pigment epithelial 19 (ARPE-19) cells and human retinal microvascular endothelial cells (HRMECs) were cultured under high-glucose conditions to simulate a diabetic environment. The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis. A diabetic rat model was induced with streptozotocin (60 mg/kg). Retinal changes, including retinal ganglion cell (RGC) apoptosis, vascular alterations, and cytokine expression, were evaluated using fundus fluorescein angiography, hematoxylin and eosin and periodic acid Schiff staining, immunofluorescence, confocal imaging, and Western blot analysis.

RESULTS

High-glucose conditions significantly increased the mRNA and protein levels of VEGF, STAT3, GFAP, and other cytokines in ARPE-19 and HRMECs. However, these levels were partially suppressed by ranibizumab. RGC apoptosis, vascular leakage, and elevated cytokine expression were observed during early-stage DR in diabetic rats. Ranibizumab treatment in diabetic rats reduced cytokine expression, restored RGCs, and repaired vascular networks.

CONCLUSION

Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway, suppresses cytokine expression, and promotes retinal repair, effectively delaying or preventing early DR progression.