PMID- 32605862
OWN - NLM
STAT- MEDLINE
DCOM- 20211124
LR  - 20211124
IS  - 1873-460X (Electronic)
IS  - 1056-8727 (Linking)
VI  - 34
IP  - 9
DP  - 2020 Sep
TI  - Increased levels of cytokines in the aqueous humor correlate with the severity of 
      diabetic retinopathy.
PG  - 107641
LID - S1056-8727(20)30400-1 [pii]
LID - 10.1016/j.jdiacomp.2020.107641 [doi]
AB  - AIMS: To determine the associations between the levels of certain cytokines in 
      the aqueous humor and the severity of diabetic retinopathy. METHODS: A total of 
      103 patients (one eye per patient) who received intravitreal injection with 
      ranibizumab for diabetic retinopathy were enrolled and divided into 3 groups: 
      nonproliferative diabetic retinopathy (NPDR) with macular edema group (42 eyes), 
      proliferative diabetic retinopathy (PDR) group (40 eyes) and neovascular glaucoma 
      due to PDR (NVG-PDR) group (21 eyes). The concentrations of interleukin (IL)-6, 
      IL-8, IL-10, vascular endothelial growth factor (VEGF), transforming growth 
      factor-beta (TGF-beta), vascular cell adhesion molecule-1 (VCAM-1), intercellular 
      adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in 
      the aqueous humor were measured. RESULTS: In this study, 42, 40 and 21 patients 
      (one eye per patient) were included in the NPDR, PDR and NVG-PDR groups, 
      respectively. The median concentrations of IL-6, IL-8, IL-10, VEGF, TGF-beta, 
      VCAM-1, ICAM-1 and MCP-1 in the groups were measured. The levels of these 8 
      cytokines increased with the severity of diabetic retinopathy, especially in the 
      NVG-PDR group. Compared with those in the NPDR group, the aqueous concentrations 
      of these 8 cytokines were higher in the PDR group and were the highest in the 
      NVG-PDR group. There were significant differences in all cytokines among the 
      three groups (P < 0.05). Multivariate analysis showed that in the NPDR and PDR 
      groups, the risk of PDR associated with elevated levels of TGF-beta (P = 0.0004, OR 
      1.11, 95% CI [1.05-1.18]) and ICAM-1 (P = 0.0408, OR 10.75, 95% CI 
      [1.10-104.61]). In the PDR and NVG groups, the risk of NVG associated with 
      elevated levels of IL-10 (P = 0.0486, OR 0.7040, 95% CI [0.4966, 0.9979]), VEGF 
      (P = 0.0279, OR 0.9963, 95% CI [0.9931, 0.9996]), and VCAM-1 (P = 0.0316, OR 
      0.9998, 95% CI [0.9996, 0.99998]). In the three groups, the risk of developing 
      NVG associated with elevated levels of TGF-beta (P < 0.001, OR 1.04, 95% CI [1.02, 
      1.05]). CONCLUSIONS: The levels of these eight cytokines in the aqueous humor 
      increased with the severity of diabetic retinopathy, especially in NVG-PDR. This 
      study suggests that TGF-beta, ICAM-1, IL-10, VEGF, and VCAM-1 may play a role in the 
      progression of diabetic retinopathy, especially TGF-beta, which may plays a 
      significant role in NVG-PDR. These cytokines potentially may be used as 
      biomarkers to predict the progress of diabetic retinopathy, contribute to the 
      choice of treatment options and/or monitor treatment responses.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Song, Shuang
AU  - Song S
AD  - Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
FAU - Yu, Xiaobing
AU  - Yu X
AD  - Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China. 
      Electronic address: yuxiaobing@sina.com.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
FAU - Dai, Hong
AU  - Dai H
AD  - Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200530
PL  - United States
TA  - J Diabetes Complications
JT  - Journal of diabetes and its complications
JID - 9204583
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 130068-27-8 (Interleukin-10)
RN  - ZL1R02VT79 (Ranibizumab)
SB  - IM
MH  - Aqueous Humor/*chemistry
MH  - Chemokine CCL2
MH  - Cytokines/*analysis
MH  - Diabetes Mellitus
MH  - *Diabetic Retinopathy/diagnosis
MH  - Glaucoma, Neovascular/diagnosis
MH  - Humans
MH  - Intercellular Adhesion Molecule-1
MH  - Interleukin-10
MH  - Interleukin-6
MH  - Interleukin-8
MH  - Macular Edema/diagnosis
MH  - Ranibizumab/therapeutic use
MH  - Transforming Growth Factor beta
MH  - Vascular Cell Adhesion Molecule-1
MH  - Vascular Endothelial Growth Factor A
OTO - NOTNLM
OT  - Aqueous humor
OT  - Cytokines
OT  - Diabetic retinopathy
OT  - Neovascular glaucoma
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      declare.
EDAT- 2020/07/02 06:00
MHDA- 2021/11/25 06:00
CRDT- 2020/07/02 06:00
PHST- 2019/11/03 00:00 [received]
PHST- 2020/05/25 00:00 [revised]
PHST- 2020/05/26 00:00 [accepted]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/11/25 06:00 [medline]
PHST- 2020/07/02 06:00 [entrez]
AID - S1056-8727(20)30400-1 [pii]
AID - 10.1016/j.jdiacomp.2020.107641 [doi]
PST - ppublish
SO  - J Diabetes Complications. 2020 Sep;34(9):107641. doi: 
      10.1016/j.jdiacomp.2020.107641. Epub 2020 May 30.