Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.

<h4>Background</h4>Diabetic retinopathy is a frequent complication of diabetes mellitus and a leading cause of blindness in adults. The objective of this study was to elucidate the diabetic retinopathy pathophysiology in more detail by comparing protein alterations in human vitreous of d...

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Main Authors: Teresa Tsai, Mohannad Alwees, Mohammad Ali Asaad, Janine Theile, Vinodh Kakkassery, H Burkhard Dick, Tim Schultz, Stephanie C Joachim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0280488
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author Teresa Tsai
Mohannad Alwees
Mohammad Ali Asaad
Janine Theile
Vinodh Kakkassery
H Burkhard Dick
Tim Schultz
Stephanie C Joachim
author_facet Teresa Tsai
Mohannad Alwees
Mohammad Ali Asaad
Janine Theile
Vinodh Kakkassery
H Burkhard Dick
Tim Schultz
Stephanie C Joachim
author_sort Teresa Tsai
collection DOAJ
description <h4>Background</h4>Diabetic retinopathy is a frequent complication of diabetes mellitus and a leading cause of blindness in adults. The objective of this study was to elucidate the diabetic retinopathy pathophysiology in more detail by comparing protein alterations in human vitreous of different diabetic retinopathy stages.<h4>Methods</h4>Vitreous samples were obtained from 116 patients undergoing pars plana vitrectomy. Quantitative immunoassays were performed of angiogenic factors (VEGF-A, PIGF, Angiopoietin-1, Angiopoietin-2, Galectin-1) as well as cytokines (IL-1β, IL-8, IFN-γ, TNF-α, CCL3) in samples from control patients (patients who don't suffer from diabetes; n = 58) as well as diabetes mellitus patients without retinopathy (n = 25), non-proliferative diabetic retinopathy (n = 12), and proliferative diabetic retinopathy patients (n = 21). In addition, correlation analysis of protein levels in vitreous samples and fasting glucose values of these patients as well as correlation analyses of protein levels and VEGF-A were performed.<h4>Results</h4>We detected up-regulated levels of VEGF-A (p = 0.001), PIGF (p<0.001), Angiopoietin-1 (p = 0.005), Angiopoietin-2 (p<0.001), IL-1β (p = 0.012), and IL-8 (p = 0.018) in proliferative diabetic retinopathy samples. Interestingly, we found a strong positive correlation between Angiopoietin-2 and VEGF-A levels as well as a positive correlation between Angiopoietin-1 and VEGF-A.<h4>Conclusion</h4>This indicated that further angiogenic factors, besides VEGF, but also pro-inflammatory cytokines are involved in disease progression and development of proliferative diabetic retinopathy. In contrast, factors other than angiogenic factors seem to play a crucial role in non-proliferative diabetic retinopathy development. A detailed breakdown of the pathophysiology contributes to future detection and treatment of the disease.
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spelling doaj.art-95542bfa2785453aad65029412d2b1a82023-01-26T05:32:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e028048810.1371/journal.pone.0280488Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.Teresa TsaiMohannad AlweesMohammad Ali AsaadJanine TheileVinodh KakkasseryH Burkhard DickTim SchultzStephanie C Joachim<h4>Background</h4>Diabetic retinopathy is a frequent complication of diabetes mellitus and a leading cause of blindness in adults. The objective of this study was to elucidate the diabetic retinopathy pathophysiology in more detail by comparing protein alterations in human vitreous of different diabetic retinopathy stages.<h4>Methods</h4>Vitreous samples were obtained from 116 patients undergoing pars plana vitrectomy. Quantitative immunoassays were performed of angiogenic factors (VEGF-A, PIGF, Angiopoietin-1, Angiopoietin-2, Galectin-1) as well as cytokines (IL-1β, IL-8, IFN-γ, TNF-α, CCL3) in samples from control patients (patients who don't suffer from diabetes; n = 58) as well as diabetes mellitus patients without retinopathy (n = 25), non-proliferative diabetic retinopathy (n = 12), and proliferative diabetic retinopathy patients (n = 21). In addition, correlation analysis of protein levels in vitreous samples and fasting glucose values of these patients as well as correlation analyses of protein levels and VEGF-A were performed.<h4>Results</h4>We detected up-regulated levels of VEGF-A (p = 0.001), PIGF (p<0.001), Angiopoietin-1 (p = 0.005), Angiopoietin-2 (p<0.001), IL-1β (p = 0.012), and IL-8 (p = 0.018) in proliferative diabetic retinopathy samples. Interestingly, we found a strong positive correlation between Angiopoietin-2 and VEGF-A levels as well as a positive correlation between Angiopoietin-1 and VEGF-A.<h4>Conclusion</h4>This indicated that further angiogenic factors, besides VEGF, but also pro-inflammatory cytokines are involved in disease progression and development of proliferative diabetic retinopathy. In contrast, factors other than angiogenic factors seem to play a crucial role in non-proliferative diabetic retinopathy development. A detailed breakdown of the pathophysiology contributes to future detection and treatment of the disease.https://doi.org/10.1371/journal.pone.0280488
spellingShingle Teresa Tsai
Mohannad Alwees
Mohammad Ali Asaad
Janine Theile
Vinodh Kakkassery
H Burkhard Dick
Tim Schultz
Stephanie C Joachim
Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
PLoS ONE
title Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
title_full Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
title_fullStr Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
title_full_unstemmed Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
title_short Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy.
title_sort increased angiopoietin 1 and 2 levels in human vitreous are associated with proliferative diabetic retinopathy
url https://doi.org/10.1371/journal.pone.0280488
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