Comparison of Gene Expression Profile of Epiretinal Membranes Obtained from Eyes with Proliferative Vitreoretinopathy to That of Secondary Epiretinal Membranes

Ryo Asato,Kazuho Ikeo,Takashi Gojobori,Yuji Oshima,Atsushi Ogura,Toshihiro Kono,Keijiro Ishikawa,Shintaro Nakao,Takahito Nakama,Yukio Sassa,Tatsuro Ishibashi,Shigeo Yoshida,Hiroshi Enaida

doi:10.1371/journal.pone.0054191

Abstract

BackgroundProliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgery which can lead to severe vision reduction by tractional retinal detachments. The purpose of this study was to determine the gene expression profile of epiretinal membranes (ERMs) associated with a PVR (PVR-ERM) and to compare it to the expression profile of less-aggressive secondary ERMs.Methodology/Principal FindingsA PCR-amplified complementary DNA (cDNA) library was constructed using the RNAs isolated from ERMs obtained during vitrectomy. The sequence from the 5′ end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs). We obtained 1116 nonredundant clusters representing individual genes expressed in PVR-ERMs, and 799 clusters representing the genes expressed in secondary ERMs. The transcriptome of the PVR-ERMs was subdivided by functional subsets of genes related to metabolism, cell adhesion, cytoskeleton, signaling, and other functions, by FatiGo analysis. The genes highly expressed in PVR-ERMs were compared to those expressed in the secondary ERMs, and these were subdivided by cell adhesion, proliferation, and other functions. Querying 10 cell adhesion-related genes against the STRING database yielded 70 possible physical relationships to other genes/proteins, which included an additional 60 genes that were not detected in the PVR-ERM library. Of these, soluble CD44 and soluble vascular cellular adhesion molecule-1 were significantly increased in the vitreous of patients with PVR.Conclusions/SignificanceOur results support an earlier hypothesis that a PVR-ERM, even from genomic points of view, is an aberrant form of wound healing response. Genes preferentially expressed in PVR-ERMs may play an important role in the progression of PVR and could be served as therapeutic targets.

Highlights

Proliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgeries [1]
All non-redundant sets of expressed sequence tags (ESTs) expressed in PVR-epiretinal membranes (ERMs) are shown in the Table S1
We examined the concentration of these two molecules, in 11 vitreous samples of patients with PVR collected during vitrectomy, and in the 26 vitreous samples obtained from patients with secondary ERM

Summary

Introduction

Proliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgeries [1]. PVR is believed to represent a maladapted retinal wound repair process with proliferation of retinal and immune cells leading to the formation of scar-like fibrous epiretinal membranes (ERMs) which can cause tractional retinal detachment (RD). Surgical removal of the fibrous membranes and restoration of the physiological conditions are the first choice treatments of PVR. The success rates of RD surgery was significantly improved by vitrectomy combined with C3F8 gas or silicone tamponade, the surgical treatment of PVR is often unsuccessful. Proliferative vitreoretinopathy (PVR) is a destructive complication of retinal detachment and vitreoretinal surgery which can lead to severe vision reduction by tractional retinal detachments. The purpose of this study was to determine the gene expression profile of epiretinal membranes (ERMs) associated with a PVR (PVR-ERM) and to compare it to the expression profile of less-aggressive secondary ERMs

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