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Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death

Delyfer, MN; Raffelsberger, W; Mercier, D; Korobelnik, JF; Gaudric, A; Charteris, DG; Tadayoni, R; ... Léveillard, T; + view all (2011) Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death. PLoS One , 6 (12) , Article e28791. 10.1371/journal.pone.0028791. Green open access

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Abstract

Background 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. Methodology/Principal Findings Statistical 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/Significance This 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.

Type: Article
Title: Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0028791
Publisher version: http://dx.doi.org/10.1371/journal.pone.0028791
Language: English
Additional information: © 2011 Delyfer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3235162
Keywords: Adult, Aged, Animals, Biological Markers, Cell Death, Down-Regulation, Gene Regulatory Networks, Humans, Inflammation, Kinetics, Mice, Middle Aged, Photoreceptor Cells, Vertebrate, Reproducibility of Results, Retinal Degeneration, Retinal Detachment, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome, Young Adult
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1415058
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