Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 7;61(2):26.
doi: 10.1167/iovs.61.2.26.

Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy

Frances Wu  1   1 , Audrey Phone  1 , Ricardo Lamy  1   1 , Dahui Ma  1   1   1 , Sawarin Laotaweerungsawat  1   1   1 , Yi Chen  1   1   1 , Tong Zhao  1   1   1 , Wei Ma  1   1   1 , Fuyan Zhang  1   1   1 , Catherine Psaras  1   1 , Jay M Stewart  1   1
Affiliations

Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy

Frances Wu et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: To investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR).

Methods: Vitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1β [MIP-1β], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection.

Results: The following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-α, MCP-1, MIP-1β, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-α, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01).

Conclusions: In this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.

PubMed Disclaimer

Conflict of interest statement

Disclosure: F. Wu, None; A. Phone, None; R. Lamy, None; D. Ma, None; S. Laotaweerungsawat, None; Y. Chen, None; T. Zhao, None; W. Ma, None; F. Zhang, None; C. Psaras, None; J.M. Stewart, None

Figures

Figure 1.
Figure 1.
Correlation of vitreous and aqueous factors in diabetic patients. There was a significant correlation between vitreous and aqueous concentrations of the cytokines IL-8, PlGF, and VEGF-A. *P < 0.05.
Figure 2.
Figure 2.
Cytokine levels among controls and diabetic patients with and without recent anti-VEGF injection. Kruskal-Wallis testing demonstrated a significant difference in vitreous and aqueous levels of all selected cytokines among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, the vitreous and aqueous VEGF-A level was decreased in patients with recent anti-VEGF injection, whereas the other cytokine levels did not change. *P < 0.0167 (Bonferroni correction).
See this image and copyright information in PMC

References

    1. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012; 366: 1227–1239. - PubMed
    1. Yu Y, Zhang J, Zhu R, et al. .. The profile of angiogenic factors in vitreous humor of the patients with proliferative diabetic retinopathy. Curr Mol Med. 2017; 17: 280–286. - PubMed
    1. Gross JG, Glassman AR, Jampol LM, et al. .. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015; 314: 2137–2146. - PMC - PubMed
    1. Vujosevic S, Simó R.. Local and systemic inflammatory biomarkers of diabetic retinopathy: an integrative approach. Invest Ophthalmol Vis Sci. 2017; 58: BIO68–BIO75. - PubMed
    1. Wykoff CC, Chakravarthy U, Campochiaro PA, Bailey C, Green K, Cunha-Vaz J. Long-term effects of intravitreal 0.19 mg fluocinolone acetonide implant on progression and regression of diabetic retinopathy. Ophthalmology. 2017; 124: 440–449. - PubMed

Publication types

Substances