Lack of Evidence for Vasoactive and Inflammatory Mediators in the Promotion of Macular Edema Associated with Epiretinal Membranes

Brooks P Applewhite,Elizabeth Wellmann,Akrit Sodhi,Gregg L Semenza,Syed Junaid Hassan,Silvia Montaner,Howard S Ying,David Poon,Savalan Babapoor-Farrokhran

doi:10.1038/s41598-017-08997-6

Abstract

The development of symptoms in patients with epiretinal membranes (ERMs) often corresponds with the accumulation of interstitial fluid in the retina [i.e., the development of macular edema, (ME)]. To explore the potential value of pharmacologic therapeutic options to treat ME in patients with ERMs, we examine here the expression of vasoactive and inflammatory mediators in the vitreous of patients with idiopathic ERMs. We observed that vitreous concentrations of classic vasoactive factors (e.g., vascular endothelial growth factor) were similar in ERM patients with ME compared to controls. Using an array assessing the expression of 102 inflammatory cytokines we similarly did not observe a marked difference in cytokine expression in the vitreous of most ERM patients with ME compared to control patients. While the array data did implicate a group of inflammatory cytokines that were elevated in a subset of ERM patients who had severe ME (central subfield thickness ≥450 μm on spectral domain optical coherence tomography), expression of 3 of these inflammatory cytokines, all previously implicated in the promotion of ME in ischemic retinal disease, were not elevated by quantitative enzyme-linked immunosorbent assay. We conclude that therapies modulating vasoactive mediators or inflammatory cytokines may not affect ME in ERM patients.

Highlights

Epiretinal membranes (ERMs) are common in the elderly population, with peak prevalence between age 70 and 791
A pathogenic link between ME associated with epiretinal membranes (ERMs) and that associated with retinal vascular disease is supported by immunohistochemical studies demonstrating expression of hypoxia-inducible factor (HIF)-1α and the HIF-1-regulated gene product, vascular endothelial growth factor (VEGF), in surgically-removed idiopathic and diabetic ERMs10–12
To assess whether HIF-1-regulated vasoactive cytokines other than VEGF could be contributing to the development of ME in ERM patients, we explored the abundance using enzyme-linked immunosorbent assays (ELISAs), of angiopoietin 2 (ANGPT2)[13] and angiopoietin-like 4 (ANGPTL4)[14, 15] in the vitreous of ERM (n = 28–31) patients compared to controls (n = 25)

Summary

Introduction

Epiretinal membranes (ERMs) are common in the elderly population, with peak prevalence (up to 1/3 of patients) between age 70 and 791. We identified 4 cytokines on the array that were present at similar concentrations in all 24 vitreous samples (including all ERM patients and control paitents) tested (eFigure 2), and may serve the purpose of vitreous “housekeeping” cytokines when assessing cytokine expression using ELISAs. Increased levels of 12 cytokines were detected in the vitreous of a subset of patients with ERMs and severe ME (Fig. 3 and eTable 4).

Results

Conclusion