Transcriptomic Analysis of Human Retinal Detachment Reveals Both Inflammatory Response and Photoreceptor Death

Marie-Noëlle Delyfer,Florence Metge,Olivier Poch,Pierre-Olivier Barale,José-Alain Sahel,David Mercier,Jean-François Korobelnik,Ramin Tadayoni,David G Charteris,Wolfgang Raffelsberger,Jean-Denis Muller,Alain Gaudric,Georges Caputo,Raymond Ripp,Thierry Léveillard

doi:10.1371/journal.pone.0028791

Abstract

BackgroundRetinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome.Methodology/Principal FindingsStatistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here.Conclusions/SignificanceThis systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

Highlights

Retinal detachment (RD) is a potentially blinding condition characterized by the subretinal accumulation of fluid in a space created between the neurosensory retina at the level of photoreceptor cells and the underlying retinal pigment epithelium (RPE)
Besides the loss of photoreceptors secondary to the detachment itself, an inflammatory response develops during RD that leads to Proliferative Vitreo-Retinopathy (PVR), a clinical outcome resulting from the formation of contractile cellular membranes on both surfaces of the retina and in the vitreous
The mechanism involved in retinal detachment at the genome level has only been addressed to date on animal models of the pathology [44,45,46]

Summary

Introduction

Retinal detachment (RD) is a potentially blinding condition characterized by the subretinal accumulation of fluid in a space created between the neurosensory retina at the level of photoreceptor cells and the underlying retinal pigment epithelium (RPE). Despite retinal reattachment after surgery, visual outcome remains below expectation in many cases and patients often report permanent alterations in colour perception and/or severe loss of visual acuity due to the loss of photoreceptor cells [2,3,4,5]. Besides the loss of photoreceptors secondary to the detachment itself, an inflammatory response develops during RD that leads to Proliferative Vitreo-Retinopathy (PVR), a clinical outcome resulting from the formation of contractile cellular membranes on both surfaces of the retina and in the vitreous. Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome

Methods

Results

Conclusion