Biomarkers for PVR in rhegmatogenous retinal detachment.

Souska Zandi,Justus G Garweg,Isabel B Pfister,Christoph Tappeiner,Magdalena Skowronska,Alain Despont,Robert Rieben,Peter G Traine,Demetrios G Vavvas

doi:10.1371/journal.pone.0214674

Souska Zandi, Justus G Garweg + Show 7 more

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https://doi.org/10.1371/journal.pone.0214674

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Abstract

PurposeVarious profibrotic and proinflammatory cytokines have been found upregulated in uncomplicated primary retinal detachment (pRD), but without providing a uniform picture. Here, we compare the cyto- and chemokine profiles in pRD with and without proliferative vitreoretinopathy (PVR) in an attempt to unravel relevant differences not in single cytokines, but in the cytokine profiles at diagnosis.MethodsUndiluted vitreous fluid (VF) was obtained at the beginning of surgery from 174 eyes with pRD without relevant PVR (maximally grade B; group 1; n = 81) and with moderate or advanced PVR requiring a gas tamponade (group 2; n = 49) or silicon oil filling (group 3; n = 44). VF of eyes undergoing macular hole (MH) surgery served as controls (group 4; n = 26). Forty-three cytokines were quantified in parallel using a multiplex cytokine analysis system (Bioplex). For all comparisons we applied Holm’s correction to control for multiple comparisons.Results44.9% of group 2 eyes presented grade C1 and 55.1% C2-C3, whereas 86.4% of group 3 eyes exhibited a PVR grade of C2-D.CCL19 was the only cytokine that displayed higher concentrations in the vitreous of eyes with PVR C1 compared to lower PVR grades. Eyes with PVR C2-D showed higher levels of CCL27, CXCL6, IL4, IL16, CXCL10, CCL8, CCL22, MIG/CXCL9, CCL15, CCL19, CCL 23 and CXCL12 compared to controls. Interestingly, no difference of cytokine levels was detected between C1 and C2-D PVR.ConclusionsCCL19 may represent a potential biomarker for early PVR progression that holds promise for future diagnostic and therapeutic applications.

Highlights

Cell-signaling mediators, such as cytokines and chemokines are involved in the regulation of inflammatory processes, wound healing and scar formation [1]
CCL19 may represent a potential biomarker for early proliferative vitreoretinopathy (PVR) progression that holds promise for future diagnostic and therapeutic applications
The majority of which did not exhibit any differences in their clinical relevance, except for IL-1, IL-6, IL-8, IL-10, TNFalpha, IL1-beta, IFN gamma, ICAM-1, PDGF, MIF and the chemokine ligands CCL2, CCL11, CCL17, CCL18, CCL19, CCL22, CXCL8, CXCL9 and CXCL10 [17,18,20]

Summary

Introduction

Cell-signaling mediators, such as cytokines and chemokines are involved in the regulation of inflammatory processes, wound healing and scar formation [1]. In eyes with retinal detachment, elevated levels of a variety of cytokines and growth factors in the vitreous have been reported [2,3,4,5,6,7]. Retinal detachment (RD) induces cell migration and proliferation as well as the production of extracellular matrix proteins, which in turn lead to the development and contraction of vitreal and periretinal membranes, both hallmarks of proliferative vitreoretinopathy (PVR) [8,9,10]. Depending on the duration and extent of RD, the accumulation of fibroblasts, collagen, and extracellular matrix components may co-occur with the formation of membranes on the vitreous and the interfaces of the entire retina, including the still attached parts. The majority of which did not exhibit any differences in their clinical relevance, except for IL-1, IL-6, IL-8, IL-10, TNFalpha, IL1-beta, IFN gamma, ICAM-1, PDGF, MIF (macrophage inhibitory factor) and the chemokine ligands CCL2, CCL11, CCL17, CCL18, CCL19, CCL22, CXCL8, CXCL9 and CXCL10 [17,18,20]

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