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ANTIANGIOGENIC ISOFORMS OF VASCULAR ENDOTHELIAL GROWTH FACTOR PREDOMINATE IN SUBRETINAL FLUID OF PATIENTS WITH RHEGMATOGENOUS RETINAL DETACHMENT AND PROLIFERATIVE VITREORETINOPATHY

Ricker, Lukas J A G MD*†; Dieudonné, Suzanne C PhD*; Kessels, Alfons G H MD; Rennel, Emma S PhD§; Berendschot, Tos T J M PhD* ; Hendrikse, Fred MD, PhD* ; Kijlstra, Aize PhD* ; La Heij, Ellen C MD, PhD*

doi: 10.1097/IAE.0b013e31821800b9
Original Study
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Background: In proliferative vitreoretinopathy (PVR), a nonangiogenic eye disease that is characterized by the formation of mainly avascular membranes, vascular endothelial growth factor (VEGF) levels are found to be upregulated. Recently, it was discovered that VEGF is alternatively spliced to form the angiogenic (VEGFxxx) and antiangiogenic (VEGFxxxb) family of isoforms. Previous studies on expression of VEGF in PVR samples have not distinguished between the two families of isoforms.

Methods: We measured total VEGF and VEGFxxxb levels in subretinal fluid of patients with PVR (n = 10) and in patients with uncomplicated rhegmatogenous retinal detachment (n = 27) using enzyme-linked immunosorbent assay.

Results: We found total VEGF levels to be 2- to 3-fold elevated in the PVR group as compared with the rhegmatogenous retinal detachment group (P = 0.047). Antiangiogenic VEGFxxxb isoforms predominated (>60% of total VEGF) in the majority of rhegmatogenous retinal detachment and PVR samples investigated, although a wide variability of isoform ratios was observed within both groups.

Conclusion: The absence of an increased ratio of VEGFxxx to VEGFxxxb in patients with PVR as compared with patients with uncomplicated rhegmatogenous retinal detachment may explain a lack of blood vessels in PVR membranes. Elevated VEGF levels indicate that this cytokine may play a role in the pathogenesis of PVR that is not related to angiogenesis.

This study showed that C levels are significantly higher in subretinal fluid samples from patients with proliferative vitreoretinopathy than in samples from patients with uncomplicated rhegmatogenous retinal detachment. The antiangiogenic isoforms of rhegmatogenous retinal detachment that predominate in the majority of samples in both groups may explain why proliferative vitreoretinopathy membranes are mainly avascular.

From the *Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht, The Netherlands; †European Graduate School for Neuroscience (EURON), Maastricht, The Netherlands; ‡Department of Clinical Epidemiology and Medical Technology Assessment, University Hospital Maastricht, Maastricht, The Netherlands; and §Department of Physiology, Preclinical Veterinary School, Microvascular Research Laboratories, University of Bristol, Bristol, UK.

S. C. Dieudonné is deceased.

The authors have no financial interest or conflicts of interest.

Reprint requests: Lukas J. A. G. Ricker, MD, Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; e-mail: l.ricker@np.unimaas.nl

© The Ophthalmic Communications Society, Inc.