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Xavier Guillonneau, David Rivera, Hugo Charles-Messance, Aida Jimenez-Corona, Aude COUTURIER, Alvaro Rendon, Jose Alain Sahel, Chiara M Eandi, Florian Sennlaub, Enrique O Graue-Hernandez, Yonathan Garfias; Monocytes from patients with diabetic retinopathy are characterized by increased VEGF transcription during early macrophage differentiation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2529. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Type 2 diabetes (T2DM) affects a growing part of the population in all developed countries. More than 60% of people with T2DM will develop a form a Diabetic Retinopathy (DR) after 20 years of diabetes. Diabetic patients demonstrate robustly elevated intravitreal levels of inflammatory cytokines. Infiltrating monocyte (Mo)-derived inflammatory Macrophages (MPs) account for most of the production of these cytokines in animal models of DR. We hypothesized that pre-activated circulating inflammatory monocytes found in T2DM are an important pathogenic factor in DR.
T2DM and control patients were enrolled and diagnosed for diabetic retinopathy. Four groups were defined as follows: (i) controls, (ii) diabetic patients with no retinopathy, (iii) patients with NPDR, and (iv) PDR patients. Patients with known history of nephropathy and periodontitis were excluded. Plasma and monocytes were collected from all groups. Fresh monocytes were allowed to differentiate into MPs for 18h and RNA and culture supernatant were collected. Fresh Monocytes and monocyte-derived MPs were then evaluated for their ability to produce cytokines known to be elevated in the vitreous of DR patients including IL-1β, IL-6, IL-8, CCL2, and VEGF
Seventy-two subjects were included. The 3 diabetic groups were evenly distributed for age, BMI, blood glucose and Hba1c. Circulating monocytes demonstrated low expression of cytokines with minor differences between groups. In contrast, upon differentiation MP increased their expression of all tested cytokines. After 18h the expression of VEGF was higher in patients with NPDR or PDR than in diabetic patients with no retinopathy.
Our data support a model in which circulating monocytes in DR patients have a greater propensity to produce inflammatory cytokines when they differentiate into inflammatory macrophages compared to T2DM patients. Understanding how monocyte derived-inflammatory cytokine influence DR and treatment outcomes might be new cues to propose innovative treatments of these pathologies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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