title: Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.
abstract: BACKGROUND
  Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats.
  
  
  METHODS
  To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis.
  
  
  RESULTS
  We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located.
  
  
  CONCLUSIONS
  Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Hong
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Choi
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Yoon
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Ahn
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University Bundang Hospital, 300 Gumi-dong, Seongnam 463-707, Korea. sejoon1@snu.ac.kr.
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Woo
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D018845:CD11 Antigens / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D037102:Lectins; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000254:growth & development* / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000473:pathology; D019700:Thrombospondin 1 / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; D016207:Cytokines; D037102:Lectins; D008070:Lipopolysaccharides; D019700:Thrombospondin 1