FEATURES OF THE OCULAR IMMUNE RESPONSE IN RABBITS WITH MECHANICAL CORNEAL INJURY AND ITS CORRECTION WITH STEM CELLS

Abstract

Introduction. Research in ophthalmology has shown the significant role of cytokines as key bioregulators of inflammatory and reparative processes in the pathogenesis of eye diseases. Aim of the Study. The aim of our study was to investigate the changes in cellular immunity indicators and the cytokine profile in the blood and aqueous humor of the anterior chamber of rabbits' eyes following a simulated mechanical non-penetrating corneal injury and treatment with Corneregel and mesenchymal stem cells (MSCs). Methods. An epithelial incision was made on the superior part of the cornea using a trephine, after which the epithelium was removed along with the anterior layer of the corneal stroma. Anesthesia was administered locally using a 0.5 % Alcaine solution and a 2 % lidocaine solution. For treatment, the preparation Corneregel and mesenchymal stem cells derived from the umbilical cord were used. The levels of CD4 and CD8 were determined by flow cytometry. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) were determined using an enzyme-linked immunosorbent assay (ELISA). The immunoregulatory index (CD4/CD8) and the inflammatory activity index ((TNF-α) + (IL-1β) + (IL-6) / (IL-10)) were also calculated. Results and Discussion. After simulating the mechanical injury, a disproportionate increase in the levels of T-helper and T-suppressor cells was observed, leading to a significant decrease in the immunoregulatory index, as well as a significant increase in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). The concentration of the anti-inflammatory cytokine (IL-10) increased less intensively in the initial stages and had decreased by day 28, which resulted in a significant increase in the inflammatory activity index. The use of corrective agents was accompanied by a less pronounced increase in cellular immunity indicators and the normalization of their ratio, as well as a significantly smaller increase in the levels of pro-inflammatory and anti-inflammatory cytokines, with the inflammatory activity index normalizing by day 28. Conclusion. In the context of mechanical corneal injury, the administration of mesenchymal stem cells effectively modulates the immune response in the eye, reduces the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and increases the level of the anti-inflammatory cytokine IL-10, thereby normalizing the level of inflammatory activity.