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Maryam Ghiassi, Brandie D. Wagner, Alan Palestine, Naresh Mandava, Anne M. Lynch; TNFa and other Select Cytokines in Patients with Intermediate Age-Related Macular Degeneration (iAMD). Invest. Ophthalmol. Vis. Sci. 2022;63(7):355 – F0186.
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© ARVO (1962-2015); The Authors (2016-present)
Age related macular degeneration (AMD) is a leading cause of blindness worldwide. The disease affects the local microenvironment of photoreceptors and retinal pigment epithelium causing an irreversible cell loss and subsequent decline in vision. It has been shown by our group that patients with iAMD have significantly altered levels of several inflammatory biomarkers, including complement factors and CCLx chemokines, in cases with iAMD compared to control patients without AMD. Building on this research that supports a role for systemic inflammation in patients with iAMD, we embarked on this study to compare levels of plasma cytokines namely, TNFa, IL-6. IL-8, IL-1ra, IL-4, and VEGF in patients with iAMD compared to controls with no AMD.
Patients with iAMD who were part of the University of Colorado IRB approved AMD registry were included in this study. Imaging studies and blood plasma samples were obtained from both iAMD and control patients. Cases and controls were defined using the Beckmann classification and multimodal imaging. The cytokine analysis was conducted using current established laboratory protocols. Wilcoxon rank-based tests were used to compare cytokine levels between the two groups.
There were 211 patients with iAMD and 100 controls. The iAMD and control groups were comparable in smoking status, BMI, hypertension, cardiac and vascular disease. We found TNFa levels to be significantly higher in cases with iAMD compared to control patients (P<0.01). Levels of IL-6, IL-8, IL-1ra, IL-4 and VEGF levels did not differ between cases and controls (Table-1).
Patients with iAMD had higher levels of TNFa, a key regulator of the inflammatory response, compared with controls. TNFa is produced by macrophages, monocytes and other cells and has been shown to have direct effects on retinal pigment epithelial cells including induction of complement expression and up-regulation of VEGF production. These findings support our hypothesis that systemic inflammatory markers can distinguish patients with and without iAMD. Serum TNFa levels can potentially be used as a biomarker to identify high risk patients with iAMD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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