Increased Angiopoietin-1 and -2 levels in human vitreous are associated with proliferative diabetic retinopathy

Abstract

Background Diabetic retinopathy is a frequent complication of diabetes mellitus and a leading cause of blindness in adults. The objective of this study was to elucidate the diabetic retinopathy pathophysiology in more detail by comparing protein alterations in human vitreous of different diabetic retinopathy stages. Methods Vitreous samples were obtained from 116 patients undergoing pars plana vitrectomy. Quantitative immunoassays were performed of angiogenic factors (VEGF-A, PIGF, Angiopoietin-1, Angiopoietin-2, Galectin-1) as well as cytokines (IL-1β, IL-8, IFN-γ, TNF-α, CCL3) in samples from control patients (patients who don’t suffer from diabetes; n = 58) as well as diabetes mellitus patients without retinopathy (n = 25), non-proliferative diabetic retinopathy (n = 12), and proliferative diabetic retinopathy patients (n = 21). In addition, correlation analysis of protein levels in vitreous samples and fasting glucose values of these patients as well as correlation analyses of protein levels and VEGF-A were performed. Results We detected up-regulated levels of VEGF-A (p = 0.001), PIGF (p<0.001), Angiopoietin-1 (p = 0.005), Angiopoietin-2 (p<0.001), IL-1β (p = 0.012), and IL-8 (p = 0.018) in proliferative diabetic retinopathy samples. Interestingly, we found a strong positive correlation between Angiopoietin-2 and VEGF-A levels as well as a positive correlation between Angiopoietin-1 and VEGF-A. Conclusion This indicated that further angiogenic factors, besides VEGF, but also pro-inflammatory cytokines are involved in disease progression and development of proliferative diabetic retinopathy. In contrast, factors other than angiogenic factors seem to play a crucial role in non-proliferative diabetic retinopathy development. A detailed breakdown of the pathophysiology contributes to future detection and treatment of the disease.

Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease

“…It has previously been reported that IL-8 is higher in adolescents with T1D and poor metabolic control, possibly providing explanation to this observation [ 43 ]. Furthermore, IL-1β and IL-8 were recently reported to be elevated together in the vitreous fluid of patients with diabetes and proliferative retinopathy [ 44 ]. Several studies report a role for GAL-1 in diabetic retinopathy, and it is possible that our observation is indicative of a shared regulation for IL-1β and IL-8 and GAL-1 in the microvascular pathophysiology of T1D [ 34 , 45 , 46 ].…”

Beyond VEGF: Angiopoietin–Tie Signaling Pathway in Diabetic Retinopathy

“…Faricimab-svoa is a heterodimeric bispecific monoclonal antibody developed using CrossMab technology that targets both VEGF-A and Ang2 [173]. CrossMab technology enables correct antibody light chain association with their respective heavy chain and thus enforcing specific heterodimerization of two different antigen binding domains [166,174].…”

The Role of Helicobacter pylori and Metabolic Syndrome-Related Mast Cell Activation Pathologies and Their Potential Impact on Pregnancy and Neonatal Outcomes

“…1.1.1. The Role of H. pylori/MetS-Related Pericyte Dysfunction Pathologies and Their Potential Impact on Pregnancy and Neonatal Outcomes Pericytes, which are implicated in H. pylori/MetS-related AH and T2DM pathophysiology [36,37], are specialized cells closely associated with the vasculature system, playing a key role in regulating endothelial cell characteristics and ensuring the constancy and preservation of blood vessels essential for normal vascular functionality [38]. The collaboration between endothelium and pericytes is critical for appropriate microvascular development, constancy, and maintenance [39,40].…”