TY - JOUR
T1 - Vitreous protein networks around ANG2 and VEGF in proliferative diabetic retinopathy and the differential effects of aflibercept versus bevacizumab pre-treatment
AU - Klaassen, Ingeborg
AU - Avery, Peter
AU - Schlingemann, Reinier O.
AU - Steel, David H. W.
N1 - Funding Information: This study was funded by grants from Stichting Blinden-Penning that contributed through UitZicht (Grant UitZicht 2017-30), Rotterdamse Stichting Blindenbelangen (Grant B20170068), Nederlandse Vereniging ter Verbetering van het Lot der Blinden, Stichting Blindenhulp. This study was also supported by a grant from Bayer Pharmaceuticals given to Newcastle University (IIR-GB-2016-2886). This study was published with the help of the Edward and Marianne Blaauw Fund for Ophthalmology. The funding organizations had no role in the design or conduct of this research. They provided unrestricted grants. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Extracellular signalling proteins interact in networks rather than in isolation. In this context we investigated vitreous protein levels, including placental growth factor (PlGF), angiopoietin-2 (ANG2) and vascular endothelial growth factor (VEGF), in patients with proliferative diabetic retinopathy (PDR) with variable disease severities, and after anti-VEGF pre-treatment. Vitreous samples of 112 consecutive patients undergoing vitrectomy for PDR and of 52 non-diabetic patients with macular holes as controls were studied. A subset of the PDR patients were treated with either aflibercept (AFB, n = 25) or bevacizumab (BVZ)/ranibizumab (RZB) (n = 13), before surgery. Antibody-based analysis of 35 proteins (growth factors and cytokines) showed a significant increase in expression levels of 27 proteins in PDR patients as compared to controls. In network analysis of co-regulated proteins, a strong correlation in expression levels between VEGF, PlGF, MCP1 and ANG2 was found, mostly clustered around ANG2. In the AFB treatment group, concentrations of several proteins were decreased, including VEGFR1, whereas interleukin 6 and 8 were increased as compared to untreated PDR patients. The observed differences in vitreous protein levels between the different treatments and untreated PDR patients may underlie differences in clinical outcomes in patients with PDR.
AB - Extracellular signalling proteins interact in networks rather than in isolation. In this context we investigated vitreous protein levels, including placental growth factor (PlGF), angiopoietin-2 (ANG2) and vascular endothelial growth factor (VEGF), in patients with proliferative diabetic retinopathy (PDR) with variable disease severities, and after anti-VEGF pre-treatment. Vitreous samples of 112 consecutive patients undergoing vitrectomy for PDR and of 52 non-diabetic patients with macular holes as controls were studied. A subset of the PDR patients were treated with either aflibercept (AFB, n = 25) or bevacizumab (BVZ)/ranibizumab (RZB) (n = 13), before surgery. Antibody-based analysis of 35 proteins (growth factors and cytokines) showed a significant increase in expression levels of 27 proteins in PDR patients as compared to controls. In network analysis of co-regulated proteins, a strong correlation in expression levels between VEGF, PlGF, MCP1 and ANG2 was found, mostly clustered around ANG2. In the AFB treatment group, concentrations of several proteins were decreased, including VEGFR1, whereas interleukin 6 and 8 were increased as compared to untreated PDR patients. The observed differences in vitreous protein levels between the different treatments and untreated PDR patients may underlie differences in clinical outcomes in patients with PDR.
UR - http://www.scopus.com/inward/record.url?scp=85143419538&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-022-25216-z
DO - https://doi.org/10.1038/s41598-022-25216-z
M3 - Article
C2 - 36473885
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 21062
ER -