Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

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Abstract

Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).

Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF- α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.

Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p < 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 ( r = 0.370 to 0.497, all p < 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 ( r = 0.370 to 0.906, all p < 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen ( r = 0.328 to 0.638, all p < 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate ( r = −0.325 to −0.603, all p < 0.05).

Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.

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Most cited references 42

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A new equation to estimate glomerular filtration rate.

Andrew Levey, Lesley Stevens, Christopher H Schmid … (2009)

Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.

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Global Prevalence and Major Risk Factors of Diabetic Retinopathy

Joanne Yau, Sophie L. Rogers, Ryo Kawasaki … (2012)

OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

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Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis.

Seth R Flaxman, Rupert Bourne, Serge Resnikoff … (2017)

Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020.

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Author and article information

Contributors

Guanrong Wu: URI : http://loop.frontiersin.org/people/1279353/overview

Baoyi Liu: URI : http://loop.frontiersin.org/people/1139059/overview

Qiaowei Wu: URI : http://loop.frontiersin.org/people/1371574/overview

Changting Tang: URI : http://loop.frontiersin.org/people/1363747/overview

Zijing Du: URI : http://loop.frontiersin.org/people/1279350/overview

Ying Fang: URI : http://loop.frontiersin.org/people/1279346/overview

Yijun Hu: URI : http://loop.frontiersin.org/people/1280113/overview

Honghua Yu: URI : http://loop.frontiersin.org/people/1279359/overview

Journal

Journal ID (nlm-ta): Front Med (Lausanne)

Journal ID (iso-abbrev): Front Med (Lausanne)

Journal ID (publisher-id): Front. Med.

Title: Frontiers in Medicine

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-858X

Publication date (Electronic): 28 September 2021

Publication date Collection: 2021

Volume: 8

Electronic Location Identifier: 727407

Affiliations

[1] ¹School of Medicine, South China University of Technology , Guangzhou, China

[2] ²Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences , Guangzhou, China

[3] ³Aier Institute of Refractive Surgery, Refractive Surgery Center, Guangzhou Aier Eye Hospital , Guangzhou, China

[4] ⁴Aier School of Ophthalmology, Central South University , Changsha, China

Author notes

Edited by: Ravirajsinh Jadeja, Augusta University, United States

Reviewed by: Dong Ho Park, Kyungpook National University Hospital, South Korea; Masahiko Sugimoto, Mie University, Japan

*Correspondence: Yijun Hu huyijun2014@ 123456163.com

Honghua Yu yuhonghua@ 123456gdph.org.cn

This article was submitted to Ophthalmology, a section of the journal Frontiers in Medicine

†These authors have contributed equally to this work and share first authorship

Article

DOI: 10.3389/fmed.2021.727407

PMC ID: 8505670

PubMed ID: 34650995

SO-VID: e0dd5e3d-c824-409b-9a40-e46f3e864660

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 18 June 2021

Date accepted : 31 August 2021

Page count

Figures: 1, Tables: 4, Equations: 0, References: 42, Pages: 8, Words: 5203

Funding

Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;

Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

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Most cited references 42

A new equation to estimate glomerular filtration rate.

Global Prevalence and Major Risk Factors of Diabetic Retinopathy

Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis.

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