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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Main Authors: Vivian Rajeswaren, 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Ophthalmology
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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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