Inhibitory effect of IL-1 antagonist on corneal vascularizations in rats

Purpose: The aim of this study was to demonstrate the effect of interleukin-1 receptor antagonist (IL-1ra) on corneal neovascularization in an experimental corneal chemical burn model. The effect of IL-1ra was compared with a control group, a placebo group, and a bevacizumab group. Materials and Methods: In this study, 40 female Wistar Albino rats were divided into 5 groups and chemically induced corneal neovascularization by applying silver nitrate sticks to both eyes. Group I served as the control group without any treatment. Group II received 0.1 ml physiological saline subconjunctivally on day 1 and day 5 under anesthesia. Group III received 0.25 mg/0.1 ml IL-1ra, Group IV received 2.5 mg/0.1 ml IL-1ra, and Group V received 2.5 mg/0.1 ml bevacizumab via subconjunctival administration. After 14 days, rat corneas were excised for pathological examination of the right eyes and for biochemical ELISA examination of the left eyes. Pathological examination involved microscopic analysis of inflammatory and vascular parameters using hematoxylin & eosin, CD34, and IL-1 alpha staining. Biochemical ELISA test measured IL-1 alpha, Transforming Growth Factor-B (TGF-B), Tumor Necrosis Factor-a (TNF-a), Vascular Endothelial Growth Factor (VEGF), and Malondialdehyde (MDA) levels. Results: According to the ELISA test results among the study groups, there was a statistically significant difference in the distribution of IL-1 alpha levels. This difference was due to higher IL-1 alpha levels in Group I rats compared to Group III, Group IV, and Group V rats (p values: p=0.001; p=0.001; p=0.001, respectively). In the distribution of VEGF levels, significant differences were observed with the lowest mean VEGF value of 101.08 in Group IV compared to Group I, Group III, and Group V rats (p values: p=0.003; p=0.040; p<0.001; p<0.001; p=0.005; p<0.001, respectively). In the pathological examination, Group IV rats had a significantly lower inflammatory membrane ratio compared to Group II and Group V rats (p values: p=0.041; p=0.005). Fibroblast proliferation was higher in Group II rats compared to Group III and Group IV rats (p values: p=0.030; p=0.045). When evaluating vascular structuring, Group I rats showed higher vascular structuring compared to Group IV and Group V rats, and Group II rats had higher vascular structuring than Group IV rats (p vii values: p=0.015; p=0.030; p=0.045). The lowest average vascular structuring score of 1.5 was observed in Group IV. Conclusion: This study demonstrated that subconjunctival IL-1 alpha receptor antagonist reduced IL-1α and VEGF levels in corneal chemical burn model as shown by ELISA. Pathological examination of corneas revealed decreased fibroblast proliferation, inflammatory, and vascular structures. As a result, the anti-angiogenic effect of IL-1α receptor antagonist was observed to be higher compared to the bevacizumab group. IL-1 alpha receptor antagonist has an inhibitory effect on corneal neovascularization secondary to inflammation.