Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy
IntroductionTumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of othe...
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Frontiers Media S.A.
2024-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fopht.2024.1356957/full |
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author | Vivian Rajeswaren Brandie D. Wagner Brandie D. Wagner Jennifer L. Patnaik Naresh Mandava Marc T. Mathias Niranjan Manoharan Talisa E. de Carlo Forest Ramya Gnanaraj Anne M. Lynch Alan G. Palestine the University of Colorado Retina Research Group |
author_facet | Vivian Rajeswaren Brandie D. Wagner Brandie D. Wagner Jennifer L. Patnaik Naresh Mandava Marc T. Mathias Niranjan Manoharan Talisa E. de Carlo Forest Ramya Gnanaraj Anne M. Lynch Alan G. Palestine the University of Colorado Retina Research Group |
author_sort | Vivian Rajeswaren |
collection | DOAJ |
description | IntroductionTumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.MethodsWe examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers.ResultsThere were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group.DiscussionThese findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development. |
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spelling | doaj.art-cac45276983e4da2963eec87a44343f82024-08-03T08:28:52ZengFrontiers Media S.A.Frontiers in Ophthalmology2674-08262024-03-01410.3389/fopht.2024.13569571356957Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophyVivian Rajeswaren0Brandie D. Wagner1Brandie D. Wagner2Jennifer L. Patnaik3Naresh Mandava4Marc T. Mathias5Niranjan Manoharan6Talisa E. de Carlo Forest7Ramya Gnanaraj8Anne M. Lynch9Alan G. Palestine10the University of Colorado Retina Research GroupDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesColorado School of Public Health, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, United StatesIntroductionTumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.MethodsWe examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers.ResultsThere were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group.DiscussionThese findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.https://www.frontiersin.org/articles/10.3389/fopht.2024.1356957/fullage-related macular degenerationtumor necrosis factor alphavascular endothelial growth factorintermediate age related macular degenerationgeographic atrophy |
spellingShingle | Vivian Rajeswaren Brandie D. Wagner Brandie D. Wagner Jennifer L. Patnaik Naresh Mandava Marc T. Mathias Niranjan Manoharan Talisa E. de Carlo Forest Ramya Gnanaraj Anne M. Lynch Alan G. Palestine the University of Colorado Retina Research Group Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy Frontiers in Ophthalmology age-related macular degeneration tumor necrosis factor alpha vascular endothelial growth factor intermediate age related macular degeneration geographic atrophy |
title | Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy |
title_full | Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy |
title_fullStr | Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy |
title_full_unstemmed | Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy |
title_short | Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy |
title_sort | elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age related macular degeneration and geographic atrophy |
topic | age-related macular degeneration tumor necrosis factor alpha vascular endothelial growth factor intermediate age related macular degeneration geographic atrophy |
url | https://www.frontiersin.org/articles/10.3389/fopht.2024.1356957/full |
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