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Erschienen in: International Ophthalmology 10/2020

15.06.2020 | Original Paper

Comparison of inflammatory cytokines levels in the aqueous humor with diabetic retinopathy

verfasst von: Haijiang Zhang, Liang Liang, Rong Huang, Ping Wu, Liye He

Erschienen in: International Ophthalmology | Ausgabe 10/2020

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Abstract

Purpose

Evidence has accumulated suggesting that various inflammatory cytokines are involved in the progress of diabetic retinopathy (DR), but there are few studies concerning the relationship between individual cytokines levels in the aqueous humor (AH) and the severity of DR. This study aimed to explore the differences of interleukin (IL)-23, IL-17, IL-10 and transforming growth factor (TGF)-β in AH form patients with different proliferative stages of DR.

Methods

From June 2016 to June 2019, patients for senile cataract surgery were enrolled with the informed consent. All cases were graded into 4 groups: the control group (patients without diabetes), non-retinopathy (NDR) group (diabetic patients without retinopathy), non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. The concentrations of IL-23, IL-17, IL-10, and TGF-β in AH were measured using ELISA and compared them within four groups by ANOVA.

Results

In this study, 20 (28.57%), 18 (25.71%), 17 (24.29%), and 15 (21.43%) patients were included in the control, NDR, NPDR, and PDR groups, respectively. There had no significant differences in demographic characteristics (P > 0.05). Comparison of these cytokines within four groups revealed: the IL-23 level was increased in NDR group initially and raised along with the progression of DR (P < 0.01). The IL-17 level was significantly higher in NPDR and PDR groups compared to NDR and the control groups, and positively correlated with more-severe DR (P < 0.01). By contrast, The IL-10 level was significantly lower in diabetic patients than in non-diabetic controls, and decreased as the severity of DR increased (P < 0.05). In addition, TGF-β was also elevated in diabetic patients, but showed no differences based on the presence or severity of DR (P > 0.05).

Conclusions

The over-expression of IL-23 and IL-17 in AH might have a synergistic effect on the pathogenesis well before the proliferative stage, and was typical positively correlated with the severity of DR. These results offer a novel early therapeutic target for DR.
Literatur
1.
Zurück zum Zitat Wong TY, Cheung CM, Larsen M, Sharma S, Simo R (2016) Diabetic retinopathy. Nat Rev Dis Primers 2:16012CrossRef Wong TY, Cheung CM, Larsen M, Sharma S, Simo R (2016) Diabetic retinopathy. Nat Rev Dis Primers 2:16012CrossRef
2.
Zurück zum Zitat Ola MS, Nawaz MI, Siddiquei MM, AI-Amro S, AbuEI-Asrar AM (2012) Recent advance in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complicat 26(1):56–64CrossRef Ola MS, Nawaz MI, Siddiquei MM, AI-Amro S, AbuEI-Asrar AM (2012) Recent advance in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complicat 26(1):56–64CrossRef
3.
Zurück zum Zitat Zhang GH, Chen HY, Chen WQ, Zhang MZ (2017) Prevalence and risk factors for diabetic retinopathy in China: a multi-hospital-based cross-sectional study. Br J Ophthalmol 101(12):1591–1595CrossRef Zhang GH, Chen HY, Chen WQ, Zhang MZ (2017) Prevalence and risk factors for diabetic retinopathy in China: a multi-hospital-based cross-sectional study. Br J Ophthalmol 101(12):1591–1595CrossRef
4.
Zurück zum Zitat Yashodhara S, Sandeep S, Arvind M, Saxena A, Natu SM (2013) Advanced glycation end products and diabetic retinopathy. J Ocul Biol Dis Infor 5(3–4):63–69 Yashodhara S, Sandeep S, Arvind M, Saxena A, Natu SM (2013) Advanced glycation end products and diabetic retinopathy. J Ocul Biol Dis Infor 5(3–4):63–69
5.
Zurück zum Zitat Kowluru RA, Kowluru A, Mishra M, Kumar B (2015) Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res 48:40–61CrossRef Kowluru RA, Kowluru A, Mishra M, Kumar B (2015) Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res 48:40–61CrossRef
6.
Zurück zum Zitat Kim JH, Kim JH, Jun KO, Yu YS, Kim KW (2010) Inhibition of protein kinase C delta attenuates blood-retinal barrier breakdown in diabetic retinopathy. Am J Pathol 176(3):1517–1524CrossRef Kim JH, Kim JH, Jun KO, Yu YS, Kim KW (2010) Inhibition of protein kinase C delta attenuates blood-retinal barrier breakdown in diabetic retinopathy. Am J Pathol 176(3):1517–1524CrossRef
7.
Zurück zum Zitat Powell ED, Field RA (1964) Diabetic retinopathy and rheumatoid arthritis. Lancet 2(7439):17–18CrossRef Powell ED, Field RA (1964) Diabetic retinopathy and rheumatoid arthritis. Lancet 2(7439):17–18CrossRef
8.
Zurück zum Zitat Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358CrossRef Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358CrossRef
9.
Zurück zum Zitat Wang W, Lo AC (2018) Diabetic retinopathy: pathophysiology and treatment. Int J Mol Sci 19(6):1816CrossRef Wang W, Lo AC (2018) Diabetic retinopathy: pathophysiology and treatment. Int J Mol Sci 19(6):1816CrossRef
10.
Zurück zum Zitat Rübsam A, Parikh S, Fort PE (2018) Role of inflammation in diabetic retinopathy. Int J Mol Sci 19(4):E942CrossRef Rübsam A, Parikh S, Fort PE (2018) Role of inflammation in diabetic retinopathy. Int J Mol Sci 19(4):E942CrossRef
11.
Zurück zum Zitat Sugimoto M, Ichio A, Kondo M (2015) Short pulse duration high-power laser photocoagulation during vitrectomy for diabetic retinopathy reduces postoperative inflammation. PLoS ONE 10(8):e0135126CrossRef Sugimoto M, Ichio A, Kondo M (2015) Short pulse duration high-power laser photocoagulation during vitrectomy for diabetic retinopathy reduces postoperative inflammation. PLoS ONE 10(8):e0135126CrossRef
12.
Zurück zum Zitat Miossec P (2009) IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect 11(5):625–630CrossRef Miossec P (2009) IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect 11(5):625–630CrossRef
13.
Zurück zum Zitat Kim BS, Park YJ, Chung Y (2016) Targeting IL-17 in autoimmunity and inflammation. Arch Pharm Res 39(11):1537–1547CrossRef Kim BS, Park YJ, Chung Y (2016) Targeting IL-17 in autoimmunity and inflammation. Arch Pharm Res 39(11):1537–1547CrossRef
14.
Zurück zum Zitat Pepple KL, Lin P (2018) Targeting interleukin-23 in the treatment of noninfectious uveitis. Ophthalmology 125(12):1977–1983CrossRef Pepple KL, Lin P (2018) Targeting interleukin-23 in the treatment of noninfectious uveitis. Ophthalmology 125(12):1977–1983CrossRef
15.
Zurück zum Zitat Isabelle S, Rainer WF, Peter A, Scherm MG, Gökmen F, Haupt F et al (2016) Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. Nat Commun 7:10991CrossRef Isabelle S, Rainer WF, Peter A, Scherm MG, Gökmen F, Haupt F et al (2016) Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. Nat Commun 7:10991CrossRef
16.
Zurück zum Zitat Mittal SK, Roche PA (2015) Suppression of antigen presentation by IL-10. Curr Opin Immunol 34:22–27CrossRef Mittal SK, Roche PA (2015) Suppression of antigen presentation by IL-10. Curr Opin Immunol 34:22–27CrossRef
17.
Zurück zum Zitat Kajdaniuk D, Markek B, Borgiel-Markek H, Kos-Kudła B (2013) Transforming growth factor β1(TGF-β1)in physiology and pathology. Endokrynol Pol 64(5):384–396CrossRef Kajdaniuk D, Markek B, Borgiel-Markek H, Kos-Kudła B (2013) Transforming growth factor β1(TGF-β1)in physiology and pathology. Endokrynol Pol 64(5):384–396CrossRef
18.
Zurück zum Zitat Cheung CM, Vania M, Ang M, Chee SP, Li J (2012) Comparison of aqueous humor cytokine and chemokine levels in diabetic patients with and without retinopathy. Mol Vis 18:830–837PubMedPubMedCentral Cheung CM, Vania M, Ang M, Chee SP, Li J (2012) Comparison of aqueous humor cytokine and chemokine levels in diabetic patients with and without retinopathy. Mol Vis 18:830–837PubMedPubMedCentral
19.
Zurück zum Zitat Wu F, Phone A, Lamy R, Ma D, Laotaweerungsawat S, Chen Y et al (2020) Correction of aqueous, vitreous, and plasma cytokine levels with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 61(2):26CrossRef Wu F, Phone A, Lamy R, Ma D, Laotaweerungsawat S, Chen Y et al (2020) Correction of aqueous, vitreous, and plasma cytokine levels with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 61(2):26CrossRef
20.
Zurück zum Zitat Xu HY, Cai M, Zhang XD (2015) Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats. Graefes Arch Clin Exp Ophthalmol 253(9):1482–1492CrossRef Xu HY, Cai M, Zhang XD (2015) Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats. Graefes Arch Clin Exp Ophthalmol 253(9):1482–1492CrossRef
21.
Zurück zum Zitat Wang Y, Fan LL, Meng XD, Jiang F, Chen QZ, Zhang ZH et al (2016) Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats. Graefes Arch Clin Exp Ophthalmol 254(10):1957–1965CrossRef Wang Y, Fan LL, Meng XD, Jiang F, Chen QZ, Zhang ZH et al (2016) Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats. Graefes Arch Clin Exp Ophthalmol 254(10):1957–1965CrossRef
22.
Zurück zum Zitat Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682CrossRef Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682CrossRef
23.
Zurück zum Zitat Feng SF, Yu HH, Yu Y, Geng Y, Li DL, Yang C et al (2018) Levels of inflammatory cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in aqueous humor of patients with diabetic retinopathy. J Diabetes Res 4:8546423 Feng SF, Yu HH, Yu Y, Geng Y, Li DL, Yang C et al (2018) Levels of inflammatory cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in aqueous humor of patients with diabetic retinopathy. J Diabetes Res 4:8546423
24.
Zurück zum Zitat Lee JH, Lee W, Kwon OH, Kim JH, Kwon OW, Kim KH et al (2008) Cytokine profile of peripheral blood in Type 2 diabetes mellitus patients with diabetic retinopathy. Ann Clin Lab Sci 38(4):361–367PubMed Lee JH, Lee W, Kwon OH, Kim JH, Kwon OW, Kim KH et al (2008) Cytokine profile of peripheral blood in Type 2 diabetes mellitus patients with diabetic retinopathy. Ann Clin Lab Sci 38(4):361–367PubMed
25.
Zurück zum Zitat Chen H, Zhang XZ, Liao NY, Wen F (2017) Assessment of biomarkers suing multiplex assays in aqueous humor of patient with diabetic retinopathy. BMC Ophthalmol 17(1):176CrossRef Chen H, Zhang XZ, Liao NY, Wen F (2017) Assessment of biomarkers suing multiplex assays in aqueous humor of patient with diabetic retinopathy. BMC Ophthalmol 17(1):176CrossRef
26.
Zurück zum Zitat Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10(7):479–489CrossRef Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10(7):479–489CrossRef
27.
Zurück zum Zitat Kawanokuchi J, Shimizu K, Nitta A, Yamada K, Mizuno T, Takeuchi H et al (2008) Production and functions of IL-17 in microglia. J Neuroimmunol 194(1–2):54–61CrossRef Kawanokuchi J, Shimizu K, Nitta A, Yamada K, Mizuno T, Takeuchi H et al (2008) Production and functions of IL-17 in microglia. J Neuroimmunol 194(1–2):54–61CrossRef
28.
Zurück zum Zitat Chen Y, Yang PZ, Li FZ, Kijlstra A (2011) The effects of Th17 cytokines on the inflammatory mediator production and barrier function of ARPE-10 cells. PLoS ONE 6(3):e18139CrossRef Chen Y, Yang PZ, Li FZ, Kijlstra A (2011) The effects of Th17 cytokines on the inflammatory mediator production and barrier function of ARPE-10 cells. PLoS ONE 6(3):e18139CrossRef
29.
Zurück zum Zitat Chan CC, Ardeljan D (2014) Molecular pathology of macrophages and interleukin-17 in age- related macular degeneration. Adv Exp Med Biol 801:193–198CrossRef Chan CC, Ardeljan D (2014) Molecular pathology of macrophages and interleukin-17 in age- related macular degeneration. Adv Exp Med Biol 801:193–198CrossRef
30.
Zurück zum Zitat Wang J, Gong HM, Liang L (2017) Correlation analysis of new inflammatory factor interleukin-17 with diabetic retinopathy. Chin J Optom Ophthalmol Vis Sci 19(7):428–431 Wang J, Gong HM, Liang L (2017) Correlation analysis of new inflammatory factor interleukin-17 with diabetic retinopathy. Chin J Optom Ophthalmol Vis Sci 19(7):428–431
31.
Zurück zum Zitat Takeuchi M, Sato T, Tanaka A, Muraoka T, Taguchi M, Sakurai Y et al (2015) Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients. PLoS ONE 9:e0137358CrossRef Takeuchi M, Sato T, Tanaka A, Muraoka T, Taguchi M, Sakurai Y et al (2015) Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients. PLoS ONE 9:e0137358CrossRef
32.
Zurück zum Zitat Wang C, You QS, Cao XS, Guo HL, Gao XX, Peng XY (2017) Micro RNA-19a suppresses interleukin-10 in peripheral B cells of patients with diabetic retinopathy. Am J Transl Res 9(3):1410–1417PubMedPubMedCentral Wang C, You QS, Cao XS, Guo HL, Gao XX, Peng XY (2017) Micro RNA-19a suppresses interleukin-10 in peripheral B cells of patients with diabetic retinopathy. Am J Transl Res 9(3):1410–1417PubMedPubMedCentral
33.
Zurück zum Zitat Mallmann F, Canani LH (2019) Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy. Afq Bras Oftalmol 82(4):275–282 Mallmann F, Canani LH (2019) Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy. Afq Bras Oftalmol 82(4):275–282
34.
Zurück zum Zitat Wu HL, Hwang DK, Song XD, Tao Y (2017) Association between aqueous cytokines and diabetic retinopathy stage. J Ophthalmol 2017:9402198PubMedPubMedCentral Wu HL, Hwang DK, Song XD, Tao Y (2017) Association between aqueous cytokines and diabetic retinopathy stage. J Ophthalmol 2017:9402198PubMedPubMedCentral
35.
Zurück zum Zitat Khuu LA, Tayyari F, Sivak JM, Flanagan JG, Singer S, Brent MH et al (2017) Aqueous humor concentrations of TGF-β and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy. Acta Ophthalmol 95(3):e206–e211CrossRef Khuu LA, Tayyari F, Sivak JM, Flanagan JG, Singer S, Brent MH et al (2017) Aqueous humor concentrations of TGF-β and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy. Acta Ophthalmol 95(3):e206–e211CrossRef
Metadaten
Titel
Comparison of inflammatory cytokines levels in the aqueous humor with diabetic retinopathy
verfasst von
Haijiang Zhang
Liang Liang
Rong Huang
Ping Wu
Liye He
Publikationsdatum
15.06.2020
Verlag
Springer Netherlands
Erschienen in
International Ophthalmology / Ausgabe 10/2020
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-020-01463-9

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