Comparison of the effects of digoxin and bevacizumab on oxygen-induced retinopathy rat model

Purpose: To evaluate the effect of digoxin on oxygen-induced retinopathy (OIR) model and compare the results with bevacizumab treatment.Methods: Twenty-eight newborn Sprague-Dawley rats were randomly divided into four groups:control group, normoxia+intraperitoneal (ip) normal saline (NS); OIR group, OIR+ip NS; OIR+digoxin group, OIR+ip 0.1 mg/kg of digoxin; and OIR+bevacizumab group, OIR+ip 2.5 mg/kg of bevacizumab.The rats were exposed to 50% oxygen for 24 h, followed by 10% oxygen for 24 h, to induce OIR.This cycle was repeated seven times until 14 days postnatal (P).In all groups, single-dose injections were administered on P15 th day.Histopathological and immunohistochemical examinations were performed at the end of the study.Results: The mean neovascular cell nuclei counts (NVCN) of the four groups were 9.00±3.16,41.80±11.44,19.38±2.20,and 16.00±2.62.The mean NVCN count was significantly reduced in the treatment groups compared to the OIR group (p<0.001).The mean NVCN count was similar between the treatment groups (p=0.078).In immunohistochemical staining, the immunoreactivity values of the vascular endothelial growth factor (VEGF) were 0.01±0.00,1.65±0.30,0.09±0.08,and 0.04±0.02,and the tumor necrosis factor alpha (TNF-α) values were 0.10±0.00,1.12±0.18,0.18±0.13,and 0.14±0.05.In the OIR group, VEGF and TNF-α immunoreactivity increased markedly compared to the control group (p<0.001).VEGF and TNF-α immunoreactivity of the treatment groups decreased significantly compared to the OIR group (p<0.001).VEGF and TNF-α immunoreactivity were similar between the treatment groups (VEGF:p=0.752;TNF-α:p=0.099).Conclusions: Retinal neovascularization was significantly suppressed by digoxin treatment, and this effect was comparable to bevacizumab in the OIR model.