Changes in AH cytokines and metabolomics in contralateral eyes of ARC patients following unilateral surgery reveal effects on the contralateral eye's intraocular environment stability

Abstract

Background: For patients with bilateral age-related cataracts, sequential phacoemulsification and intraocular lens implantation is a common treatment. However, it remains unclear whether surgery on the first eye affects the outcome of the second eye, as current research results are inconsistent. This study will explore whether surgery on one eye affects the non-operated eye by analyzing changes in aqueous humor biomarkers and metabolomics in the second eye. Methods: A rabbit model of unilateral phacoemulsification and intraocular lens implantation was established. The experimental group consisted of 15 rabbits undergoing this procedure. Postoperatively, rabbits were divided into five subgroups (three rabbits per subgroup), and aqueous humor was collected from both the operated and non-operated eyes at 1 day, 3 days, 1 week, 2 weeks, and 3 weeks after surgery. Additionally, 5 rabbits were selected as a control group, from which aqueous humor was extracted. Levels of IL-1a, IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, TNF-α, MCP-1, and VEGF in the aqueous humor were compared. In the clinical study, preoperative aqueous humor samples were collected from 22 patients undergoing bilateral phacoemulsification and intraocular lens implantation. Among them, 11 patients were tested for the aforementioned 10 cytokines, while the other 11 patients underwent untargeted metabolomics research. Results: In the animal experiment, levels of all 10 cytokines in the operated eyes were significantly higher compared to both the control and non-operated eyes groups (P < 0.05). In the non-operated eyes, IL-1β and IL-2 levels were also elevated compared to the control (P < 0.05). IL-1β remained elevated at 3 weeks post-surgery, while IL-2 returned to baseline after 3 days.In the clinical study, no significant differences were found in cytokine levels between the two eyes.In the untargeted metabolomics analysis, 354 metabolites showed differential expression—280 were upregulated and 74 were downregulated. Notably, Adenine and 2-Aminopurine were significantly downregulated, highlighting Purine metabolism as the most impacted pathway. Conclusions: Animal experiments showed a significant increase in IL-1β and IL-2 levels in the non-operated eyes postoperatively, reflecting systemic and local inflammatory responses. In clinical experiments, although no significant changes in cytokines were observed in the aqueous humor of both eyes, differential expression of metabolites indicated metabolic adjustments in the non-operated eye following surgery on the first eye. These findings suggest potential metabolic effects of surgery on the non-operated eye at the metabolic level.