Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders

Maria D Pinazo-Durán,1,* Carmen Galbis-Estrada,1,* Sheila Pons-Vázquez,1 Jorge Cantú-Dibildox,2 Carla Marco-Ramírez,1 Javier Benítez-del-Castillo21Ophthalmic Research Unit Santiago Grisolia, Department of Surgery/Ophthalmology, Faculty of Medicine, University of Valencia, Valencia, Spain; 2Department of Ophthalmology, Hospital of Jerez, Jerez de la Frontera, Spain*These authors contributed equally to this workBackground: Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs).Objective: To analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs.Methods: We used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not ( NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program.Results: Significantly higher expressions of interleukin (IL)-1β, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1β, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1β, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG-NS and in the CG+S versus the CG-NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG-NS.Conclusion: IIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined formulation of antioxidant and EPUFAs supplementation. Our findings may be considered for future protocols integrating clinical/biochemical d