Molecular mechanism of the effect of anakinra on experimentally induced ocular ischemic syndrome in rats

Aim: To investigate the biochemical and histopathological effects of anakinra on possible retinal damage induced by bilateral clamping and unclamping of the common carotid arteries in rats, and to evaluate these effects in comparison with Tocilizumab. Materials and Methods: In this study, 24 male albino Wistar rats were used. The animals were divided into four groups: the sham-operated group (SG), the group subjected to bilateral common carotid cross-clamping and unclamping (CUG), the anakinra + common carotid cross-clamping and unclamping group (ACU), and the tocilizumab + common carotid cross-clamping and unclamping group (TCU). At the end of the experimental period, the rats were euthanized under high-dose anesthesia, and malondialdehyde (MDA), total glutathione (tGSH), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were measured in the extracted ocular tissues. Additionally, retinal tissues were examined histopathologically. Results: Our biochemical findings demonstrated that bilateral clamping and unclamping of the common carotid arteries in rats led to an increase in oxidant and pro-inflammatory cytokine levels in ocular tissue, accompanied by a decrease in antioxidant levels. Histopathological analyses also confirmed that the I/R procedure induced ocular ischemic syndrome (OIS). Anakinra significantly prevented the I/R-related increase in oxidants and pro-inflammatory cytokines, the reduction in antioxidants, as well as the associated morphological alterations in the ocular tissue. These results clearly indicate that anakinra may be an effective and promising therapeutic option for preventing OIS-related tissue damage. The originality of this study lies in being the first experimental research evaluating the effects of anakinra on OIS. Conclusion: It has been demonstrated that anakinra reduces oxidative stress, inflammation, and histopathological damage in the experimental ocular ischemic syndrome model, and histopathological findings indicate that it is effective in preventing OIS-related tissue injury.