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Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
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Year : 2012  |  Volume : 19  |  Issue : 1  |  Page : 70-74  

Role of inflammation in the pathogenesis of diabetic retinopathy

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Web Publication20-Jan-2012

Correspondence Address:
Ahmed M Abu El-Asrar
Department of Ophthalmology, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411
Saudi Arabia
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Source of Support: Medical Research Chair funded by Dr. Nasser Al-Rasheed, Conflict of Interest: None

DOI: 10.4103/0974-9233.92118

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Diabetic retinopathy (DR) remains a major cause of worldwide preventable blindness. The microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, including activation of protein kinase C, increased advanced glycation end products formation, polyol pathway, and oxidative stress, and activation of the renin angiotensin system (RAS). There is an accumulating body of evidence that inflammation plays a prominent role in the pathogenesis of DR.

Keywords: Angiogenesis, diabetic retinopathy, inflammation

How to cite this article:
Abu El-Asrar AM. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol 2012;19:70-4

How to cite this URL:
Abu El-Asrar AM. Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol [serial online] 2012 [cited 2023 Feb 5];19:70-4. Available from: http://www.meajo.org/text.asp?2012/19/1/70/92118

   Introduction Top

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide among adults aged 20-74 years. The two most important visual complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). The prevalence of DR increases with duration of diabetes, and mostly all persons with type 1 diabetes and more than 60% of those with type 2 have some form of retinopathy after 20 years. According to Wisconsin epidemiologic study of diabetic retinopathy (WESDR), 3.6% of younger-onset patients (type 1diabetes) and 1.6% of older-onset patients (type 2 diabetes) were legally blind. [1]

Inflammation is a nonspecific response to injury that includes a variety of functional and molecular mediators, including recruitment and activation of leukocytes. Many of the molecular and functional changes that are characteristic of inflammation have been detected in retinas from diabetic animals or humans, and in retinal cells under diabetic conditions.

A large body of evidence supports the role of proinflammatory cytokines, chemokines and other inflammatory mediators in the pathogenesis of diabetic retinopathy leading to persistent low grade inflammation, and influx of leukocytes contributing to damage to the retinal vasculature and neovascularization. The causal relationship between inflammation and angiogenesis is now widely accepted. [2] An emerging issue in diabetic retinopathy research is the focus on the mechanistic link between activation of subclinical inflammation and angiogenesis.

Leukostasis, a major component of inflammatory processes, increases significantly in the retinas of diabetic animals and may contribute to capillary nonperfusion in DR. [3],[4] Leukostasis has been postulated to be a factor in endothelial cell deaths and breakdown of the blood-retinal barrier. Increased permeability of the blood retinal barrier occurs in patients with diabetes, contributing to retinal edema and visual impairment. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are associated with leukocyte recruitment and adhesion to the retinal vasculature which correlate with increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and elevated expression of the b-integrin subunit CD18 on neutrophils. [3],[4] Joussen et al,[3] reported that retinas from diabetic mice lacking ICAM-1 and CD18 are protected from the development of diabetes-induced increase in leukostasis, vascular permeability, and degeneration of retinal capillaries. Therefore, these proteins/receptors are important in the development of early stages of DR.

In addition, the increased expression of many inflammatory proteins are regulated at the level of gene transcription through the activation of proinflammatory transcription factors including NF-kB, specificity protein 1 (SP1), activator protein 1 (AP-1) and peroxisome proliferator-activated receptors (PPARs). [5] A large body of evidence suggested the involvement of several inflammatory molecules in the pathogenesis of DR including proinflammatory cytokines such as TNF-α, interleukin-1 b (IL-1b), and interleukin-6 (IL-6) and chemokines such as MCP-1, interferon-g-inducible protein of 10 kDa (IP-10), stromal cell derived factor-1 (SDF-1), and interleukin-8 (IL-8) in addition to other key inflammatory proteins including inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9/gelatinase B).

Increased levels of TNFα have been found in the vitreous fluid of diabetic patients [6] and a strong correlation between plasma levels of TNF-α and severity of DR has been reported. [7] An association between the serum level of TNF-α and PDR in type 1 diabetes has also been demonstrated. [7] We have shown the expression of TNF-α in vascular endothelial cells and stromal cells in epiretinal membranes due to PDR, supporting a link between low grade inflammation and PDR. [8] Several studies demonstrated that the expression of TNF-α is increased in the retina of diabetic rats [9] and that blockade of TNF-α reduced leukocyte adhesion, suppressed blood retinal barrier breakdown and reduced ICAM-1 expression. [9] High serum levels of TNF-α in a diabetic patient complicated with retinopathy and/or nephropathy have been shown to induce endothelial dysfunction. [10] In addition, increased levels of TNF-α in diabetic plasma has been shown to induce leukocyte-endothelial cell adhesion. [11] Increased vascular TNF-α expression in animal models of diabetes induced NADPH oxidase and production of reactive oxygen species leading to endothelial dysfunction. [12],[13] In vivo studies demonstrated that TNF-α enhances angiogenesis. [14] In addition, a recent study showed that TNF- α is required for VEGF-induced endothelial hyperpermeability. [15] Increased levels of IL-1b are detected in the vitreous fluid of patients with PDR [6] and in the retina of diabetic rats. [16] Increased levels of interleukin-6 (IL-6) are detected in vitreous fluid of patients with PDR and diabetic macular edema. [17],[18],[19]

Increased CCL2/MCP-1 chemokine has been reported in vitreous humor samples from patients with PDR and diabetic macular edema. [18],[19],[20],[21],[22] We have shown the expression of MCP-1 in myofibroblasts and in the vascular endothelial cells of epiretinal membranes in PDR. [20] Several studies have demonstrated that MCP-1 is a potent inducer of angiogenesis and fibrosis. [23],[24],[25] Our research and that of others indicate increased levels of CXCL10 / IP-10 in the vitreous humor samples from patients with PDR. [20],[21] Several studies have reported that IP-10 is a potent inhibitor of angiogenesis and may have an inhibitory effect on fibrosis. [26],[27] Elevated levels of IP-10 in the vitreous humor of patients with PDR, and the interaction with its receptor CXCR3 may negatively regulate fibrosis/angiogenesis in proliferative vitreoretinal disorders. [20]

CXCL12/SDF-1 is the predominant chemokine which is upregulated in many damaged tissues as part of the response to injury and mobilizes stem/progenitor cells to promote repair. Butler et al,[28] reported increased SDF-1 levels in vitreous from patients with PDR. We have demonstrated the expression of SDF-1 and its receptor CXCR4 in PDR epiretinal membranes . [20],[29] SDF-1 is upregulated in ischemic tissue establishing an SDF-1 gradient favoring recruitment of endothelial progenitor cells (EPCs) from peripheral blood to ischemic sites, thereby accelerating neovascularization. In addition, SDF-1 promotes the chemotaxis of bone marrow derived CD34+ stem cells and their differentiation into EPCs in ischemic tissue and in tumors. [30],[31],[32] Recently, Reddy et al,[31] demonstrated that upregulation of SDF-1 in tumor results in the formation of enlarged lumen-bearing functional blood vessels, implying that this chemokine may influence vascular remodeling via direct action on endothelial cells. They also showed that SDF-1 mediated vasculogenesis may represent an alternative pathway that could be utilized by tumors to sustain growth and expansion of neovascularization after anti-vascular endothelial growth factor therapy. [31]

Several recent studies have shown that interaction of SDF-1 with its receptor CXCR4 plays an important role in EPC migration, differentiation, proliferation and survival. [30],[31],[32] IL-8 is an inflammatory and angiogenic mediator that is produced by numerous cells. The vitreous levels of IL-8 were significantly higher in patients with PDR in comparison to control subjects [22] and in patients with higher extents of large vessel gliotic obliteration. [33]

Increasing evidence strongly supports the role of COX-2 and its metabolic products like prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) as regulators of angiogenesis. [34] Recent studies revealed that diabetes is associated with the upregulation of COX-2 both in large vessels and microvessels. [35] Recently, we have demonstrated that COX-2 is specifically localized in vascular endothelial cells and stromal cells in PDR epiretinal membranes, [36] which is consistent with the finding that hypoxia increases COX-2 mRNA and protein with subsequent PGE2 induction in human vascular endothelial cells. [37] In retina of diabetic animals, induction of COX-2 as well as increased production of prostaglandin E2 has been reported. [38],[39] Several studies demonstrated that PGE2 stimulated the expression of VEGF mRNA and protein and tube-like formation in endothelial cells [40] and treatments of endothelial cells with VEGF, induced the expression of COX-2 mRNA and proteins and increased PGE2 synthesis [40] suggesting a positive feedback loop for angiogenesis in endothelial cells. These findings suggest that COX-2 might provide the mechanistic link between chronic, low-grade inflammation and angiogenesis in diabetic retinopathy.

We have shown increased expression of inducible nitric oxide synthase (iNOS) in the retina of human subjects with diabetes. [41],[42] Similarly, other investigators have demonstrated expression of iNOS in retina of diabetic animals. [38] Recently, Leal et al,[43] demonstrated that the iNOS isoform plays a predominant role in leukostasis and blood-retinal barrier breakdown. The mechanism involves ICAM-1 upregulation and tight junction protein downregulation. In addition, diabetic mice deficient in iNOS did not develop leukostasis, superoxide generation, degeneration of retinal capillaries and cell loss in the ganglion cell layer. [44]

Du et al,[38] demonstrated that NOS and COX-2 act together to contribute to retinal cell death in diabetes and to the development of diabetic retinopathy. Recent animal studies by Chan et al,[45] demonstrated that good glycemic control that followed a period of poor glycemic control failed to reverse elevations in the pro-inflammatory mediators IL-1b, TNF-α, ICAM-1, vascular cell adhesion molecule 1, and iNOS in the retina of diabetic rats. Their findings suggest that failure to reverse retinal inflammatory mediators support their important role in the resistance of retinopathy to halt after cessation of hyperglycemia. [45]

High-mobility group box-1 protein (HMGB1) or amphoterin is a nonhistone DNA-binding nuclear protein that is highly conserved during evolution and is present in most eukaryotic cells where it stabilizes nucleosome formation and facilitates transcription. Necrotic cell death can result in passive leakage of HMGB1 from the cell as the protein is then no longer bound to DNA. In addition, HMGB1 can be actively secreted by different cell types, including activated monocytes and macrophages, mature dendritic cells, natural killer cells and endothelial cells. Extracellular HMGB1 functions as a proinflammatory cytokine. In addition to advanced glycation end products in diabetes, HMGB1 signals through the receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily of receptors, leading to activation of the transcription factor nuclear factor kappa B (NF-kB) and induces the expression of various leukocyte adhesion molecules and proinflammatory cytokines and chemokines. [2],[46],[47],[48] Several studies demonstrated that the HMGB1 / RAGE signaling axis is involved in angiogenic [49],[50],[51],[52] and fibrotic [53],[54],[55] disorders. Recently, we reported that HMGB1 and RAGE were expressed by vascular endothelial cells and stromal cells in PDR fibrovascular epiretinal membranes and that there were significant correlations between the level of vascularization in PDR epiretinal membranes and the expression of HMGB1 and RAGE. [56] We demonstrated elevated levels of HMGB1 in the vitreous fluid from patients with PDR and significant correlations between levels of HMGB1 and the levels of the inflammatory biomarkers MCP-1 and soluble ICAM-1. In addition, HMGB1 expression was upregulated in the retinas of diabetic mice. [57]

The development of PDR is a multistage event including angiogenesis in which basement membrane degradation, endothelial cell migration and proliferation followed by capillary tube formation occur. Such migratory and tissue remodeling events are regulated by proteolysis mediated by matrix metalloproteinases (MMPs) and other proteases. Giebel et al,[58] showed elevated levels of MMP-2/gelatinase A, and MMP-9/gelatinase B in the retinas of diabetic animals. They demonstrated that elevated expression of MMPs in the retina may facilitate an increase in vascular permeability. Several studies showed the expression of MMP-2 and MMP-9 in PDR epiretinal membranes. [59],[60] Immunohistochemical studies demonstrated immunoreactivity for MMP-9 in vascular endothelial cells and myofibroblasts in epiretinal membranes due to PDR, and in situ zymography confirmed the presence of intense gelatinolytic activity in vascular endothelial cells and in scattered cells in PDR epiretinal membranes. [59] In addition, elevated levels of MMP-9 were measured in vitreous from patients with PDR. [61],[62],[63] Recently, we demonstrated that activated MMP-9 might be involved in hemorrhagic transformation in patients with PDR. [63]

   Acknowledgement Top

The author thanks Ms. Connie B. Unisa-Marfil for secretarial work. This work was supported by Medical Research Chair funded by Dr. Nasser Al-Rasheed.

   References Top

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4 JQ1 inhibits high glucose-induced migration of retinal microglial cells by regulating the PI3K/AKT signaling pathway
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Mathematical Biosciences and Engineering. 2022; 19(12): 13079
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5 A Compressive Review on Novel Molecular Target of Diabetic Nephropathy
Astha Jaiswal, Bhupesh Chandra Semwal, Sonia Singh
Research Journal of Pharmacy and Technology. 2022; : 1398
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6 miRNA signatures in diabetic retinopathy and nephropathy: delineating underlying mechanisms
Prabhsimran Kaur, Sushil Kotru, Sandeep Singh, Anjana Munshi
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7 Administration of Melatonin in Diabetic Retinopathy Is Effective and Improves the Efficacy of Mesenchymal Stem Cell Treatment
Samraa H. Abdel-Kawi, Khalid S. Hashem, Yi Zhang
Stem Cells International. 2022; 2022: 1
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8 The Usefulness of Monocyte-to-High Density Lipoprotein and Neutrophil-to-Lymphocyte Ratio in Diabetic Macular Edema Prediction and Early anti-VEGF Treatment Response
Duygu Yalinbas Yeter, Serap Eroglu, Baris Sariakcali, Erman Bozali, Ayse Vural Ozec, Haydar Erdogan
Ocular Immunology and Inflammation. 2021; : 1
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9 Prediction of diabetic retinopathy in patients with type 2 diabetes mellitus by using monocyte to high-density lipoprotein-cholesterol ratio
Burak Erdem, Yasemin Kaya
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10 Anti-inflammatory Effect of Curcumin, Homotaurine, and Vitamin D3 on Human Vitreous in Patients With Diabetic Retinopathy
Mariaelena Filippelli, Giuseppe Campagna, Pasquale Vito, Tiziana Zotti, Luca Ventre, Michele Rinaldi, Silvia Bartollino, Roberto dell'Omo, Ciro Costagliola
Frontiers in Neurology. 2021; 11
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11 Outcome of Single Dexamethasone Implant Injection in the Treatment of Persistent Diabetic Macular Edema After Anti-VEGF Treatment: Real-Life Data from a Tertiary Hospital in Jordan
Motasem Al-Latayfeh, Mohammad Abdel Rahman, Raed Shatnawi
Clinical Ophthalmology. 2021; Volume 15: 1285
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12 Myocardial repolarization is affected in patients with diabetic retinopathy
Journal of Surgery and Medicine. 2021; 5(7): 683
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13 Elevated NLRP3 Inflammasome Levels Correlate With Vitamin D in the Vitreous of Proliferative Diabetic Retinopathy
Li Lu, Gaocheng Zou, Li Chen, Qianyi Lu, Mian Wu, Chunxia Li
Frontiers in Medicine. 2021; 8
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14 The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease
Siva S.R. Iyer, Mollie K. Lagrew, Stephanie M. Tillit, Ramak Roohipourmoallai, Samuel Korntner
International Journal of Molecular Sciences. 2021; 22(13): 7142
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15 Serum Glycoproteomic Alterations in Patients with Diabetic Retinopathy
Ashok Sharma, James Cox, Joshua Glass, Tae Jin Lee, Sai Karthik Kodeboyina, Wenbo Zhi, Lane Ulrich, Zachary Lukowski, Shruti Sharma
Proteomes. 2020; 8(3): 25
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16 Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway
Fatema Al-Rashed, Sardar Sindhu, Hossein Arefanian, Ashraf Al Madhoun, Shihab Kochumon, Reeby Thomas, Sarah Al-Kandari, Abdulwahab Alghaith, Texy Jacob, Fahd Al-Mulla, Rasheed Ahmad
Cells. 2020; 9(8): 1892
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17 Local and systemic production of 45 cytokines in complicated proliferative diabetic retinopaty
V. V. Neroev, O. V. Zaytseva, N. V. Balatskaya, A. A. Lazutova
Medical Immunology (Russia). 2020; 22(2): 301
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18 A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells
Manuel Saenz de Viteri, María Hernandez, Valentina Bilbao-Malavé, Patricia Fernandez-Robredo, Jorge González-Zamora, Laura Garcia-Garcia, Nahia Ispizua, Sergio Recalde, Alfredo Garcia-Layana
Antioxidants. 2020; 9(9): 828
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19 Vitamin D Protects against Oxidative Stress and Inflammation in Human Retinal Cells
Patricia Fernandez-Robredo, Jorge González-Zamora, Sergio Recalde, Valentina Bilbao-Malavé, Jaione Bezunartea, Maria Hernandez, Alfredo Garcia-Layana
Antioxidants. 2020; 9(9): 838
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20 The Correlation between Hemoglobin A1c (HbA1c) and Hyperreflective Dots (HRD) in Diabetic Patients
Bing Seng Wong, Sharanjeet Sharanjeet-Kaur, Nor Fariza Ngah, Rajan Rajasudha Sawri
International Journal of Environmental Research and Public Health. 2020; 17(9): 3154
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21 The cells involved in the pathological process of diabetic retinopathy
Songtao Yang, Jiaoyue Zhang, Lulu Chen
Biomedicine & Pharmacotherapy. 2020; 132: 110818
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22 Nitric oxide and TNF-a are correlates of diabetic retinopathy independent of hs-CRP and HbA1c
Pegah Khaloo, Reihane Qahremani, Soghra Rabizadeh, Mohammad Omidi, Armin Rajab, Firouzeh Heidari, Ghasem Farahmand, Masoume Bitaraf, Hossein Mirmiranpour, Alireza Esteghamati, Manouchehr Nakhjavani
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23 Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy
Rebekah Robinson, Mukund Srinivasan, Arul Shanmugam, Alexander Ward, Veena Ganapathy, Justin Bloom, Ashok Sharma, Shruti Sharma
Redox Biology. 2020; 34: 101574
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24 Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex
Wayne Huey-Herng Sheu, Keng-Hung Lin, Jun-Sing Wang, De-Wei Lai, Wen-Jane Lee, Fu-Yu Lin, Po-Hsun Chen, Cheng-Hsu Chen, Hsiang-Yu Yeh, Sheng-Mao Wu, Chin-Chang Shen, Maw-Rong Lee, Shing-Hwa Liu, Meei-Ling Sheu
Arteriosclerosis, Thrombosis, and Vascular Biology. 2020;
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25 The Protective Roles of Folic Acid in Preventing Diabetic Retinopathy Are Potentially Associated with Suppressions on Angiogenesis, Inflammation, and Oxidative Stress
Xun-Wen Lei, Qiang Li, Jin-Zhi Zhang, Yue-Mei Zhang, Yang Liu, Ke-Hu Yang
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26 Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema
Edoardo Midena, Alessandra Micera, Luisa Frizziero, Elisabetta Pilotto, Graziana Esposito, Silvia Bini
Scientific Reports. 2019; 9(1)
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27 Specialized pro-resolving mediators in diabetes: novel therapeutic strategies
Eoin P. Brennan, Muthukumar Mohan, Darrell Andrews, Madhura Bose, Phillip Kantharidis
Clinical Science. 2019; 133(21): 2121
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28 Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin-induced diabetic rats
Tian Niu, Mengya Zhao, Yan Jiang, Xindan Xing, Xin Shi, Lu Cheng, Huiyi Jin, Kun Liu
The FASEB Journal. 2019; 33(12): 13346
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29 MiR-455-5p ameliorates HG-induced apoptosis, oxidative stress and inflammatory via targeting SOCS3 in retinal pigment epithelial cells
Pan Chen, Ying Miao, PuJun Yan, Xiao Jie Wang, ChunXia Jiang, Yi Lei
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30 Curcumin inhibits high glucose-induced inflammatory injury in human retinal pigment epithelial cells through the ROS-PI3K/AKT/mTOR signaling pathway
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31 Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema
Hermelino O. Neto, Caio V. Regatieri, Mário J. Nobrega, Cristina Muccioli, Antonio M. Casella, Rafael E. Andrade, Mauricio Maia, Vinicius Kniggendorf, Magno Ferreira, André C. Branco, Rubens Belfort
Ophthalmic Surgery, Lasers and Imaging Retina. 2017; 48(9): 734
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32 Expression of wild-type p53-induced phosphatase 1 in diabetic epiretinal membranes
Jiping Xu, Haibin Zhong, Ling Cui, Qianqian Lan, Lifei Chen, Wenjing He, Yu Wu, Li Jiang, Hui Huang, Xin Zhao, Li Li, Siming Zeng, Min Li, Fan Xu
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33 Protective effect of Aster tataricus extract on retinal damage on the virtue of its antioxidant and anti-inflammatory effect in diabetic rat
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34 Role of endocannabinoids in the progression of diabetic retinopathy
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35 Proteome analysis of retinal glia cells-related inflammatory cytokines in the aqueous humour of diabetic patients
Stela Vujosevic,Alessandra Micera,Silvia Bini,Marianna Berton,Graziana Esposito,Edoardo Midena
Acta Ophthalmologica. 2016; 94(1): 56
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36 Effect of Korean Red Ginseng treatment on the gene expression profile of diabetic rat retina
Hana Yang,Gun Woo Son,Hye Rim Park,Seung Eun Lee,Yong Seek Park
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37 Epoxygenated Fatty Acids Inhibit Retinal Vascular Inflammation
Megan E. Capozzi, Sandra S. Hammer, Gary W. McCollum, John S. Penn
Scientific Reports. 2016; 6(1)
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38 Genetic Investigation of Complement Pathway Genes in Type 2 Diabetic Retinopathy: An Inflammatory Perspective
Ming Ming Yang,Jun Wang,Hong Ren,Yun Duan Sun,Jiao Jie Fan,Yan Teng,Yan Bo Li
Mediators of Inflammation. 2016; 2016: 1
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39 New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy
Young Gun Park,Young-Jung Roh
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40 The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study
Adolfo Daniel Rodríguez-Carrizalez,José Alberto Castellanos-González,Esaú César Martínez-Romero,Guillermo Miller-Arrevillaga,Fermín Paul Pacheco-Moisés,Luis Miguel Román-Pintos,Alejandra Guillermina Miranda-Díaz
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41 Relation of Serum and Vitreous Concentrations of Fetuin-A with Diabetic Retinopathy
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42 Use of the Monocyte-to-Lymphocyte Ratio to Predict Diabetic Retinopathy
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43 The Role of Microglia in Diabetic Retinopathy
Jeffery G. Grigsby,Sandra M. Cardona,Cindy E. Pouw,Alberto Muniz,Andrew S. Mendiola,Andrew T. C. Tsin,Donald M. Allen,Astrid E. Cardona
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44 Progress and protective effect of H2S on the pathogenesis of diabetic retinopathy
Yang Q, Li DH
International Eye Science. 2014; 14(1): 67-70
45 Research advances on pigment epithelium derived factor of resisting oxidative stress in diabetic retinopathy
Zhao CH, Lü HB, Zhou Q
International Eye Science. 2014; 14(4): 657-659
46 Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways
Aldebasi YH, Aly SM, Rahmani AH
International Journal of Physiology, Pathophysiology and Pharmacology. 2013; 5(4): 194-202
47 Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy
Ates O, Bilen H, Keles S, Civelekler M, Baykal O
International Journal of Ophthalmology. 2013; 6(5): 675-679
48 Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic patients
Wang, J. and Yang, M.M. and Li, Y.B. and Liu, G.D. and Teng, Y. and Liu, X.M.
Mediators of Inflammation. 2013; 2013(748435)
49 The ERK1/2 inhibitor U0126 attenuates diabetes-induced upregulation of MMP-9 and biomarkers of inflammation in the retina
Mohammad, G. and Mairaj Siddiquei, M. and Imtiaz Nawaz, M. and Abu El-Asrar, A.M.
Journal of Diabetes Research. 2013; 2013(658548)
50 High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina
Mohammad, G. and Siddiquei, M.M. and Othman, A. and Al-Shabrawey, M. and Abu El-Asrar, A.M.
Experimental Eye Research. 2013; 107: 101-109
51 High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina
Ghulam Mohammad,Mohammad Mairaj Siddiquei,Amira Othman,Mohamed Al-Shabrawey,Ahmed M. Abu El-Asrar
Experimental Eye Research. 2013; 107: 101
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52 Hyperreflective Intraretinal Spots in Diabetics without and with Nonproliferative Diabetic Retinopathy: An In Vivo Study Using Spectral Domain OCT
Stela Vujosevic,Silvia Bini,Giulia Midena,Marianna Berton,Elisabetta Pilotto,Edoardo Midena
Journal of Diabetes Research. 2013; 2013: 1
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53 The Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina
Ghulam Mohammad,Mohammad Mairaj Siddiquei,Mohammad Imtiaz Nawaz,Ahmed M. Abu El-Asrar
Journal of Diabetes Research. 2013; 2013: 1
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54 Association ofCFHandCFBGene Polymorphisms with Retinopathy in Type 2 Diabetic Patients
Jun Wang,Ming Ming Yang,Yan Bo Li,Guo Dong Liu,Yan Teng,Xiao Min Liu
Mediators of Inflammation. 2013; 2013: 1
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55 Usefulness of the Vitreous Fluid Analysis in the Translational Research of Diabetic Retinopathy
Olga Simó-Servat,Cristina Hernández,Rafael Simó
Mediators of Inflammation. 2012; 2012: 1
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56 Role of matrix metalloproteinase-2 and -9 in the development of diabetic retinopathy
Ghulam Mohammad,Mohammad Mairaj Siddiquei
Journal of Ocular Biology, Diseases, and Informatics. 2012; 5(1): 1
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57 Study progress of cytokine in diabetic retinopathy
Wang, X.-Q. and Xie, Q.
International Eye Science. 2012; 12(12): 2312-2314
58 Usefulness of the vitreous fluid analysis in the translational research of diabetic retinopathy
Simó-Servat, O. and Hernández, C. and Simó, R.
Mediators of Inflammation. 2012; 2012(872978)
59 Role of matrix metalloproteinase-2 and -9 in the development of diabetic retinopathy
Mohammad, G. and Siddiquei, M.M.
Journal of Ocular Biology, Diseases, and Informatics. 2012; 5(1): 1-8


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