title: Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: INSERM, U968, Paris, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Delyfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Raffelsberger
authors.forename: David
authors.initials: D
authors.lastname: Mercier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Korobelnik
authors.forename: Alain
authors.initials: A
authors.lastname: Gaudric
authors.forename: David G
authors.initials: DG
authors.lastname: Charteris
authors.forename: Ramin
authors.initials: R
authors.lastname: Tadayoni
authors.forename: Florence
authors.initials: F
authors.lastname: Metge
authors.forename: Georges
authors.initials: G
authors.lastname: Caputo
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Barale
authors.forename: Raymond
authors.initials: R
authors.lastname: Ripp
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Muller
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Thierry
authors.initials: T
authors.lastname: Léveillard
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death; D015536:Down-Regulation / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007700:Kinetics; D051379:Mice; D008875:Middle Aged; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology; D012163:Retinal Detachment / Q000150:complications / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers