title: Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function.
abstract: OBJECTIVE
  Perinatal inflammatory stress in preterm babies is associated with increased rates of severe retinopathy of prematurity (ROP) and adverse neurological dysfunction. In this study, we set out to determine the consequences of severe systemic inflammatory stress on developmental retinal vascularization and evaluate the subsequent outcome on retinal function in later life.
  
  
  METHODS
  Systemic inflammatory stress was induced in C57BL/6J mouse pups by an intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg) at postnatal day 4. In response to LPS, retinal inflammation was confirmed by quantitative RT-PCR analysis of diverse inflammatory markers. A detailed and systematic analysis of retinal microglial infiltration, retinal vascular morphology, density, and growth rate was performed at key time points throughout retinal vascularization. Retinal function in adult life was assessed by using electroretinography at 6 weeks postinjection.
  
  
  RESULTS
  As early as 48 hours after intraperitoneal administration of LPS, a significant increase in retinal vascular density was noted throughout the retina. A pronounced increase in the number of activated microglial cell was observed in the retinal ganglion cell layer and in the outer plexiform layer just prior to their vascularization; direct physical contact between activated microglia and sprouting vessels suggested that microglia partake in promoting the aberrant retinal vascularization. With maturity, animals subjected to perinatal inflammatory stress displayed depleted retinal vascular beds and had significantly decreased retinal function as determined by electroretinography.
  
  
  CONCLUSIONS
  Our data reveal that early severe postnatal inflammatory stress leads to abnormal retinal vascular development and increased vessel anastomosis and, ultimately, permanently compromises retinal function. The aberrant and initially exaggerated retinal vascularization observed is associated with microglial activation, providing a cellular mechanism by which perinatal sepsis predisposes to ROP.
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tremblay
authors.forename: Khalil
authors.initials: K
authors.lastname: Miloudi
authors.forename: Samaneh
authors.initials: S
authors.lastname: Chaychi
authors.forename: Sandra
authors.initials: S
authors.lastname: Favret
authors.forename: François
authors.initials: F
authors.lastname: Binet
authors.forename: Anna
authors.initials: A
authors.lastname: Polosa
authors.forename: Pierre
authors.initials: P
authors.lastname: Lachapelle
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005500:Follow-Up Studies; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012165:Retinal Ganglion Cells / Q000473:pathology*; D015861:Retinal Neovascularization / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
keywords: angiogenesis; inflammation; microglia retina; sepsis