Research progress of cytokines in vitreous of diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wen Dejia , Ren Xinjun , Zheng Chuanzhen , He Ye , Wang Qiong , Hong Yaru ,  Li Xiaorong

Tianjin Medical University Hospital, Tianjin Medical University Eye Institute, School of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China;

Corresponding author：

Li Xiaorong, Email: lixiaorong@tmu.edu.cn

Keywords：

Diabetic retinopathy; Vitreous body; Cytokines; Review

DOI：

10.3760/cma.j.issn.1005-1015.2020.02.016

Video：

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Abstract Full text Figures/Tables Video References Cited by

Blood-retina barrier destruction, nerve injury, formation of neovascularization and fibroblast proliferation membrane are important pathological changes of DR, which are related to the combined effects of various vitreous cytokines. VEGF is mainly involved in increasing retinal vascular permeability and inducing neovascularization. Pigment epithelium derived factor is vital reducing vascular permeability and neuroprotection; IL plays a key role in mediating inflammatory response. TNF-α is related to inflammation, which is significantly up-regulated by hypoxia. TGF-β is an important cytokine regulating cell proliferation and differentiation. Connective tissue growth factor can promote the growth, migration and adhesion of endothelial cell. In addition, many other molecular mechanisms have not been fully elucidated, and further study on the molecular mechanism of DR is urgent. With the further study of molecular mechanism, the early intervention and targeted treatment of DR will be more effective.

Citation： Wen Dejia, Ren Xinjun, Zheng Chuanzhen, He Ye, Wang Qiong, Hong Yaru, Li Xiaorong. Research progress of cytokines in vitreous of diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(2): 151-155. doi: 10.3760/cma.j.issn.1005-1015.2020.02.016 Copy

1.	温德佳, 任新军, 东莉洁, 等. 应用iTRAQ蛋白组技术筛选增生性糖尿病视网膜病变防治靶点的研究[J]. 中华眼科杂志, 2019, 55(10): 769-776. DOI: 10.3760/cma.j.issn.0412-4081.2019.10.008.Wen DJ, Ren XJ, Dong LJ, et al. New exploration of treatment target for proliferative diabetic retinopathy based on iTRAQ LC-MS/MS proteomics[J]. Chin J Ophthalmol, 2019, 55(10): 769-776. DOI: 10.3760/cma.j.issn.0412-4081.2019.10.008.
2.	Loukovaara S, Nurkkala H, Tamene F, et al. Quantitative proteomics analysis of vitreous humor from diabetic retinopathy patients[J]. J Proteome Res, 2015, 14(12): 5131-5143. DOI: 10.1021/acs.jproteome.5b00900.
3.	Wei Q, Zhang T, Jiang R, et al. Vitreous fibronectin and fibrinogen expression increased in eyes with proliferative diabetic retinopathy after intravitreal anti-VEGF therapy[J]. Invest Ophthalmol Vis Sci, 2017, 58(13): 5783-5791. DOI: 10.1167/iovs.17-22345.
4.	Miao H, Hou X, Hwang DK, et al. Vascular endothelial growth factor, basic fibroblast growth factor, and pigment epithelium-derived factor expression in the neovascular iris in retinal diseases[J/OL]. J Ophthalmol, 2018, 2018: 8025951[2018-04-11]. https://dx.doi.org/10.1155/2018/8025951. DOI: 10.1155/2018/8025951.
5.	Simo R, Sundstrom JM, Antonetti DA. Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy[J]. Diabetes Care, 2014, 37(4): 893-899. DOI: 10.2337/dc13-2002.
6.	Osaadon P, Fagan XJ, Lifshitz T, et al. A review of anti-VEGF agents for proliferative diabetic retinopathy[J]. Eye (Lond), 2014, 28(5): 510-520. DOI: 10.1038/eye.2014.13.
7.	Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, et al. Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases[J]. Growth Factors, 2018, 36(1-2): 48-57. DOI: 10.1080/08977194.2018.1477140.
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10.	Mecollari V, Nieuwenhuis B, Verhaagen J. A perspective on the role of class Ⅲ semaphorin signaling in central nervous system trauma[J]. Front Cell Neurosci, 2014, 8: 328. DOI: 10.3389/fncel.2014.00328.
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24.	Vigneswara V, Berry M, Logan A, et al. Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury[J]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2624-2633. DOI: 10.1167/iovs.13-11803.
25.	Leung KW, Barnstable CJ, Tombran-Tink J. Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling[J]. Mol Immunol, 2009, 46(7): 1374-1386. DOI: 10.1016/j.molimm.2008.12.001.
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27.	Liu Y, Biarnes Costa M, Gerhardinger C. IL-1beta is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1beta autostimulation[J/OL]. PLoS One, 2012, 7(5): 36949[2012-05-16]. http://dx.plos.org/10.1371/journal.pone.0036949. DOI: 10.1371/journal.pone.0036949.
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1. 温德佳, 任新军, 东莉洁, 等. 应用iTRAQ蛋白组技术筛选增生性糖尿病视网膜病变防治靶点的研究[J]. 中华眼科杂志, 2019, 55(10): 769-776. DOI: 10.3760/cma.j.issn.0412-4081.2019.10.008.Wen DJ, Ren XJ, Dong LJ, et al. New exploration of treatment target for proliferative diabetic retinopathy based on iTRAQ LC-MS/MS proteomics[J]. Chin J Ophthalmol, 2019, 55(10): 769-776. DOI: 10.3760/cma.j.issn.0412-4081.2019.10.008.
2. Loukovaara S, Nurkkala H, Tamene F, et al. Quantitative proteomics analysis of vitreous humor from diabetic retinopathy patients[J]. J Proteome Res, 2015, 14(12): 5131-5143. DOI: 10.1021/acs.jproteome.5b00900.
3. Wei Q, Zhang T, Jiang R, et al. Vitreous fibronectin and fibrinogen expression increased in eyes with proliferative diabetic retinopathy after intravitreal anti-VEGF therapy[J]. Invest Ophthalmol Vis Sci, 2017, 58(13): 5783-5791. DOI: 10.1167/iovs.17-22345.
4. Miao H, Hou X, Hwang DK, et al. Vascular endothelial growth factor, basic fibroblast growth factor, and pigment epithelium-derived factor expression in the neovascular iris in retinal diseases[J/OL]. J Ophthalmol, 2018, 2018: 8025951[2018-04-11]. 10.1155/2018/8025951">https://dx.doi.org/10.1155/2018/8025951. DOI: 10.1155/2018/8025951.
5. Simo R, Sundstrom JM, Antonetti DA. Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy[J]. Diabetes Care, 2014, 37(4): 893-899. DOI: 10.2337/dc13-2002.
6. Osaadon P, Fagan XJ, Lifshitz T, et al. A review of anti-VEGF agents for proliferative diabetic retinopathy[J]. Eye (Lond), 2014, 28(5): 510-520. DOI: 10.1038/eye.2014.13.
7. Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, et al. Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases[J]. Growth Factors, 2018, 36(1-2): 48-57. DOI: 10.1080/08977194.2018.1477140.
8. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele[J]. Nature, 1996, 380(6573): 435-439. DOI: 10.1038/380435a0.
9. Goto F, Goto K, Weindel K, et al. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels[J]. Lab Invest, 1993, 69(5): 508-517.
10. Mecollari V, Nieuwenhuis B, Verhaagen J. A perspective on the role of class Ⅲ semaphorin signaling in central nervous system trauma[J]. Front Cell Neurosci, 2014, 8: 328. DOI: 10.3389/fncel.2014.00328.
11. Marneros AG. Increased VEGF-A promotes multiple distinct aging diseases of the eye through shared pathomechanisms[J]. EMBO Mol Med, 2016, 8(3): 208-231. DOI: 10.15252/emmm.201505613.
12. Zhang F, Tang Z, Hou X, et al. VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis[J]. Proc Natl Acad Sci USA, 2009, 106(15): 6152-6157. DOI: 10.1073/pnas.0813061106.
13. Zhong X, Huang H, Shen J, et al. Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation[J]. Mol Vis, 2011, 17: 492-507.
14. Kinoshita S, Noda K, Saito W, et al. Vitreous levels of vascular endothelial growth factor-B in proliferative diabetic retinopathy[J]. Acta Ophthalmol, 2016, 94(6): 521-523. DOI: 10.1111/aos.12969.
15. Huang H, He J, Johnson D, et al. Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1alpha-VEGF pathway inhibition. diabetes 2015;64:200-212[J]. Diabetes, 2015, 64(3): 1067. DOI: 10.2337/db15-er03.
16. Kowalczuk L, Touchard E, Omri S, et al. Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy[J/OL]. PLoS One, 2011, 6(3): 17462[2011-03-07]. 10.1371/journal.pone.0017462">http://dx.plos.org/10.1371/journal.pone.0017462. DOI: 10.1371/journal.pone.0017462.
17. Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, et al. Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: current research and future perspectives[J]. Cytokine Growth Factor Rev, 2018, 39: 102-115. DOI: 10.1016/j.cytogfr.2017.11.005.
18. Zhu XF, Zou HD. PEDF in diabetic retinopathy: a protective effect of oxidative stress[J/OL]. J Biomed Biotechnol, 2012, 2012: 580687[2012-04-10]. http://europepmc.org/article/MED/22570532. DOI: 10.1155/2012/580687.
19. Katakami N, Kaneto H, Yamasaki Y, et al. Increased serum pigment epithelium-derived factor levels in type 1 diabetic patients with diabetic retinopathy[J]. Diabetes Res Clin Pract, 2008, 81(1): 4-7. DOI: 10.1016/j.diabres.2008.03.009.
20. Sheikpranbabu S, Haribalaganesh R, Banumathi E, et al. Pigment epithelium-derived factor inhibits advanced glycation end-product-induced angiogenesis and stimulates apoptosis in retinal endothelial cells[J]. Life Sci, 2009, 85(21-22): 719-731. DOI: 10.1016/j.lfs.2009.09.015.
21. Zhang SX, Wang JJ, Gao G, et al. Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor[J]. Faseb J, 2006, 20(2): 323-325. DOI: 10.1096/fj.05-4313fje.
22. Wang Y, Lu Q, Gao S, et al. Pigment epithelium-derived factor regulates glutamine synthetase and l-glutamate/l-aspartate transporter in retinas with oxygen-induced retinopathy[J]. Curr Eye Res, 2015, 40(12): 1232-1244. DOI: 10.3109/02713683.2014.990639.
23. Shen X, Xie B, Cheng Y, et al. Effect of pigment epithelium derived factor on the expression of glutamine synthetase in early phase of experimental diabetic retinopathy[J]. Ocul Immunol Inflamm, 2011, 19(4): 246-254. DOI: 10.3109/09273948.2011.580073.
24. Vigneswara V, Berry M, Logan A, et al. Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury[J]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2624-2633. DOI: 10.1167/iovs.13-11803.
25. Leung KW, Barnstable CJ, Tombran-Tink J. Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling[J]. Mol Immunol, 2009, 46(7): 1374-1386. DOI: 10.1016/j.molimm.2008.12.001.
26. Koleva-Georgieva DN, Sivkova NP, Terzieva D. Serum inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF have influence on the development of diabetic retinopathy[J]. Folia Med (Plovdiv), 2011, 53(2): 44-50. DOI: 10.2478/v10153-010-0036-8.
27. Liu Y, Biarnes Costa M, Gerhardinger C. IL-1beta is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1beta autostimulation[J/OL]. PLoS One, 2012, 7(5): 36949[2012-05-16]. 10.1371/journal.pone.0036949">http://dx.plos.org/10.1371/journal.pone.0036949. DOI: 10.1371/journal.pone.0036949.
28. Chen H, Zhang X, Liao N, et al. Assessment of biomarkers using multiplex assays in aqueous humor of patients with diabetic retinopathy[J]. BMC Ophthalmol, 2017, 17(1): 176. DOI: 10.1186/s12886-017-0572-6.
29. Takeuchi M, Sato T, Tanaka A, et al. Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients[J/OL]. PLoS One, 2015, 10(9): 0137358[2015-09-09]. 10.1371/journal.pone.0137358">http://dx.plos.org/10.1371/journal.pone.0137358. DOI: 10.1371/journal.pone.0137358.
30. Wakabayashi Y, Usui Y, Okunuki Y, et al. Increases of vitreous monocyte chemotactic protein 1 and interleukin 8 levels in patients with concurrent hypertension and diabetic retinopathy[J]. Retina, 2011, 31(9): 1951-1957. DOI: 10.1097/IAE.0b013e31820d3cee.
31. Schoenberger SD, Kim SJ, Shah R, et al. Reduction of interleukin 8 and platelet-derived growth factor levels by topical ketorolac, 0.45%, in patients with diabetic retinopathy[J]. JAMA Ophthalmol, 2014, 132(1): 32-37. DOI: 10.1001/jamaophthalmol.2013.6203.
32. Raczynska D, Lisowska KA, Pietruczuk K, et al. The level of cytokines in the vitreous body of severe proliferative diabetic retinopathy patients undergoing posterior vitrectomy[J]. Curr Pharm Des, 2018, 24(27): 3276-3281. DOI: 10.2174/1381612824666180926110704.
33. Relvas LJ, Bouffioux C, Marcet B, et al. Extracellular nucleotides and interleukin-8 production by ARPE cells: potential role of danger signals in blood-retinal barrier activation[J]. Invest Ophthalmol Vis Sci, 2009, 50(3): 1241-1246. DOI: 10.1167/iovs.08-1902.
34. Lee JH, Lee W, Kwon OH, et al. Cytokine profile of peripheral blood in type 2 diabetes mellitus patients with diabetic retinopathy[J]. Ann Clin Lab Sci, 2008, 38(4): 361-367.
35. Mao C, Yan H. Roles of elevated intravitreal IL-1beta and IL-10 levels in proliferative diabetic retinopathy[J]. Indian J Ophthalmol, 2014, 62(6): 699-701. DOI: 10.4103/0301-4738.136220.
36. Canataroglu H, Varinli I, Ozcan AA, et al. Interleukin (IL)-6, interleukin (IL)-8 levels and cellular composition of the vitreous humor in proliferative diabetic retinopathy, proliferative vitreoretinopathy, and traumatic proliferative vitreoretinopathy[J]. Ocul Immunol Inflamm, 2005, 13(5): 375-381. DOI: 10.1080/09273940490518900.
37. Skopinski P, Rogala E, Duda-Krol B, et al. Increased interleukin-18 content and angiogenic activity of sera from diabetic (type 2) patients with background retinopathy[J]. J Diabetes Complications, 2005, 19(6): 335-338. DOI: 10.1016/j.jdiacomp.2005.02.008.
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