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

Marie-Noëlle Delyfer (1, 2, 3) , Wolfgang Raffelsberger (4) , David Mercier (5) , Jean-François Korobelnik (3, 6) , Alain Gaudric (7) , David G. Charteris (8) , Ramin Tadayoni (7) , Florence Metge (9) , Georges Caputo (9) , Pierre-Olivier Barale (10) , Raymond Ripp (4) , Jean-Denis Muller (5) , Olivier Poch (4) , José-Alain Sahel (11, 9, 10) , Thierry Léveillard (11)

1 Institut de la Vision
2 Inserm U968/CNRS UMR7210/UPMC UM80 - Equipe 14 - Inflammation dans la dégénérescence neuronale et le remodelage vasculaire
3 Unité Rétine, Uvéite et Neuro-Ophtalmologie
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 LIMA (CEA, LIST) - Laboratoire Information, Modèles, Apprentissage (CEA, LIST)
6 Epidémiologie et Biostatistique [Bordeaux]
7 Département Ophtalmologie
8 VRE - Vitreo-retinal Unit
9 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
10 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
11 Institut de la Vision

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.

Mots clés: death of photoreceptor cells; Retinal detachment; immune response; inflammation; neurodegeneration; degeneration; PKD2L1; histocompatibility; gene HLA-C; transcriptome of human retinal tissues; SLCO4A1; pharmacological target; therapeutic strategy; photoreceptor damage; retinal surgery; statistical analysis

Domaines: Génétique; Organes des sens; Applications [stat.AP]; Méthodologie [stat.ME]

Marie-Noëlle Delyfer, Wolfgang Raffelsberger, David Mercier, Jean-François Korobelnik, Alain Gaudric, et al.. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.. PLoS ONE, 2011, 6 (12), pp.e28791. ⟨10.1371/journal.pone.0028791⟩. ⟨inserm-00665567⟩