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Nikhil Kenneth Mandava, Vanessa Tirado, Matthew D. Geiger, Jennifer Patnaik, Ashley Frazer-Abel, Anne Lynch, Naresh Mandava, Alan Palestine, Michael Holers, Brandie D Wagner, Idaira Sanchez-Santos, Daniela Meizner, Hugo Quiroz-Mercado, Jesse Smith; Plasma and Vitreous Complement Levels in Humans with Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6552. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Proteomic and genetic studies have implicated complement system dysregulation in diabetic retinopathy (DR) pathogenesis. The purpose of this case-controlled study was to examine the role of the complement system in patients with proliferative diabetic retinopathy (PDR). To determine the relationships between local and systemic complement activation, we examined a panel of 16 complement factors in paired samples of vitreous humor and plasma.
Patients with type 2 diabetes (T2D) undergoing pars plana vitrectomy (PPV) for tractional retinal detachment from PDR were recruited; controls included T2D patients undergoing PPV for macular hole/pucker without PDR. Subjects were excluded if they had comorbidities of the retina, vitreous hemorrhage, had recent laser treatment or anti-VEGF injections, or had previous ocular surgeries other than cataract. Plasma and vitreous samples were obtained at the time of surgery.Complement pathway protein, regulator, and activation fragment measurements were completed using two methods. Ba and C3a levels were measured by ELISA (Quidel Corp, San Diego CA, USA). The remaining measurements (C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, Factor B, Factor D, Factor H, Factor I, MBL, and Properdin) were performed by multiplex Luminex immunoassays (MilliporeSigma, Burlington MA, USA). The technician was masked to the case-control status of each subject.
A total of 18 subjects with PDR and 9 controls without PDR were analyzed. Sixty percent of recruited patients were female. PDR cases were significantly younger than controls; however, age among cases was not correlated with complement levels in the plasma or vitreous. No significant difference in plasma complement factor levels between cases and controls was found (Table 1). In marked contrast, all complement factors measured in the vitreous were significantly higher for cases compared to controls (Table 2).
Subjects with PDR have increased levels of all measured complement factors in vitreous fluid as compared to controls, including activation fragments at biologically relevant levels. No observed difference in systemic activation when comparing plasma levels suggests that widespread local complement alterations result from multiple activation pathways and effector mechanisms, contributing to subsequent retinal inflammation and injury.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Table 1. Plasma complement levels
Table 2. Vitreous complement levels
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