Purchase this article with an account.
James G. Carter, David O. Bates, Amanda J. Churchill; Changes In VEGF-A Splicing Ratios In Vitreous And Venous Plasma Of Diabetic Patients. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5951.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Proliferative diabetic retinopathy (PDR) is characterised by pathological neovascularisation mediated by vascular endothelial factor (VEGF). VEGF is alternatively spliced to both pro-angiogenic (VEGFxxx) and anti-angiogenic isoforms (VEGFxxxb family). The vitreous ratio of VEGFxxx:VEGFxxxb switches from anti-angiogenic dominance in non-diabetic patients to a pro-angiogenic environment in patients with PDR. The purpose of this study was to assess this ratio within diabetic patient groups, and investigate the relationship with circulating VEGF.
Eight patients with PDR and eleven diabetic patients without proliferative disease undergoing first-time vitrectomy surgery were recruited to the study. All patients were of Caucasian descent and were fully consented in accordance with the Declaration of Helsinki.Vitrectomy samples were collected by needle aspiration biopsy. Venous plasma samples were collected just prior to eye surgery by venepuncture. Samples were assessed for concentrations of VEGF isoforms by ELISA.
Vitreous samples showed increased concentrations (pg/υg of protein) of both VEGFxxx (7.5±1.6) and VEGFxxxb (7.0±1.8) in non-proliferative patients than those with PDR. In circulating plasma, concentrations of VEGFxxxb were no different in proliferative and non-proliferative patients, however patients with PDR had a much higher concentration of VEGFxxx vs. non-proliferatives. In both vitreous and plasma samples, the ratio of VEGFxxx to VEGFxxxb was increased in PDR patients compared to diabetic patients without proliferative disease (Vitreous: 78.1% vs. 57.1%, p=0.0683, Plasma: 81.1% vs. 56.1%, p=0.0171). However, no significant correlation between vitreous and plasma VEGFxxx:VEGFxxxb ratios was observed (r = 0.104).
Increases in favour of a pro-angiogenic environment were associated with proliferative diabetic retinopathy in a diabetic population. Individual VEGF isoform concentrations were highly variable, indicating that the balance between pro- and anti-angiogenic variants is critical in assessing the contribution of VEGF to neovascularisation.
This PDF is available to Subscribers Only