Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples

Adamiec-Mroczek, Joanna; Oficjalska−Młyńczak, Jolanta; Misiuk-Hojło, Marta

doi:10.1016/j.cyto.2009.11.004

Cited by 74 publications

(59 citation statements)

References 30 publications

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“…inflammation-mediated events in DR. 36,37 Such events may lead to retinal vascular cells and tight junctions becoming compromised, 38,39 which can lead to vascular leakage. Inflammatory molecules, such as tumor necrosis factor-a, IL-1b, IL-6, IL-8, intracellular adhesion molecule-1, vascular cell adhesion molecule 1, integrin b-2 (CD-18), and monocyte chemoattractant protein-1, play pivotal roles in the pathogenesis of DR lesions.…”

Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

170

147

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Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy. (Am J Pathol 2017, 187: 9e19; http://dx

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Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

170

147

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“…43,44 Vitreous levels of IL-1b, IL-6, and TNFa are elevated in patients with PDR, 45,46 and we also demonstrated that vitreous IL-4, IL-6, IL-17A, IL-21, IL-22, IL-31, and TNFa are up-regulated in PDR compared with ERM or macular hole. 47 Because vitrectomy was performed during the remission phase of systemic and intraocular inflammation in most of the ocular sarcoidosis patients in this study, this may partially explain why their vitreous TNFa levels were lower compared with that of patients with PDR.…”

Section: Discussionmentioning

confidence: 56%

Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Takeuchi

Taguchi

Sato

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines. RESULTS. High-mobility group box-1 was detected in the vitreous of 23 of 24 patients (95.8%) with ocular sarcoidosis. Mean vitreous level of HMGB1 was the highest in the sarcoidosis group, followed by the PDR and ERM groups, with significant differences between the three groups. In the sarcoidosis group, vitreous levels of IL-6, IL-10, IL-31, IFN-c, sCD40L, and TNFa were significantly higher than those in the idiopathic ERM group, and IFN-c and sCD40L were significantly higher than those in the PDR group. Vitreous HMGB-1 level correlated significantly with IL-10, IFN-c, and sCD40L levels but not with IL-6, IL-17, IL-31, or TNFa levels.CONCLUSIONS. The vitreous level of HMGB1 is elevated in ocular sarcoidosis and is associated with vitreous levels of Th1-and regulatory T-related cytokines, but not with proinflammatory or Th17-related cytokines.

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“…Previous studies of cases with macular hole and epiretinal membrane have found that among intravitreal cytokines, the levels of IL-6 [3,4], IL-8 [3,4], IL-13 [4], IP-10 [4], MCP-1 [4], MIP-1β [4], PDGF-BB [4], and VEGF [1,2,3,4,5,6,7] were higher in patients with diabetic retinopathy. We divided the patients in our current study into 2 groups based on the intravitreal VEGF level, as it was considered likely that the same type of diabetic retinopathy would be more active in patients with elevated VEGF than in those with a low level of VEGF.…”

Section: Discussionmentioning

confidence: 99%

“…Vascular endothelial growth factor (VEGF) and inflammatory cytokines are believed to be involved in the pathological process. Previous studies in patients with proliferative diabetic retinopathy (PDR) have shown that the intravitreal levels of VEGF [1,2,3,4,5,6,7], interleukin (IL)-6 [3,4], IL-8 [3,4], matrix metalloproteinase-9 [5], angiopoietin-2 [5], erythropoietin [6,8,9,10,11], platelet-derived growth factor (PDGF) [12], endothelin-1 [7,13], monocyte chemotactic protein 1 (MCP-1) [3,4,8,14], transforming growth factor beta 1 [5], and tumor necrosis factor alpha (TNF-α) [7] were elevated, while the levels of hepatocyte growth factor [15] and pigment epithelium-derived factor [16] were reduced.…”

Section: Introductionmentioning

confidence: 99%

Level of Vascular Endothelial Growth Factor in the Vitreous Fluid of Proliferative Diabetic Retinopathy Patients and Prognosis after Vitrectomy

Suzuki

Kudo

et al. 2016

Ophthalmologica

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Purpose: The aim of this study was to evaluate the relationship between the intravitreal vascular endothelial growth factor (VEGF) level and prognosis of proliferative diabetic retinopathy (PDR). Methods: The study involved 136 eyes of 114 PDR patients who underwent an initial vitrectomy between 2006 and 2008. Intravitreal VEGF levels were determined using Bio-Plex® (Bio-Rad), with levels of 5,000 pg/mL or more classified as high-VEGF (45 eyes) and levels lower than 5,000 pg/mL as low-VEGF (91 eyes). Diabetic control, PDR severity, and frequency of postoperative complications were compared between the groups. Results: There was no significant difference in preoperative status between the groups. In the low-VEGF group, a reoperation was required due to postoperative complications in 2 eyes (2.2%); 1 with vitreous hemorrhage (VH) and 1 with retinal detachment (RD). In contrast, a reoperation was required in 8 eyes (17.8%) in the high-VEGF group; 3 with VH, 2 with RD, and 3 with neovascular glaucoma. The difference between the groups was significant. There was a statistically lower postoperative corrected visual acuity logMAR (6 months after surgery) in the high-VEGF than in the low-VEGF group (p = 0.02, unpaired t test). Conclusion: Current findings indicate that careful observation is needed in patients with elevated VEGF levels.

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Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples

Cited by 74 publications

References 30 publications

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Association of High-Mobility Group Box-1 With Th Cell–Related Cytokines in the Vitreous of Ocular Sarcoidosis Patients

Level of Vascular Endothelial Growth Factor in the Vitreous Fluid of Proliferative Diabetic Retinopathy Patients and Prognosis after Vitrectomy

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