title: Choroidal involution is a key component of oxygen-induced retinopathy.
abstract: OBJECTIVE
  Retinopathy of prematurity (ROP) is a major cause of visual handicap in the pediatric population. To date, this disorder is thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies in patients with mild or moderate ROP and in the oxygen-induced retinopathy (OIR) model in rats reveal central photoreceptor disruption that overlies modest retinal vessel loss; a paucity of retinal vasculature occurs predominantly at the periphery. Given that choroidal circulation is the major source of oxygen and nutrients to the photoreceptors, the authors set out to investigate whether the choroidal vasculature system may be affected in OIR.
  
  
  METHODS
  Rat models of OIR treating newborn animals with 80% or 50/10% alternated oxygen level for the first two postnatal weeks were used to mimic ROP in humans. Immunohistology staining and vascular corrosion casts were used to investigate the vessel layout of the eye. To investigate the effect of 15-deoxy-Δ12,14-PGJ(2) (15d-PGJ(2); a nonenzymatic product of prostaglandin D(2)) on endothelial cells, in vitro cell culture and ex vivo choroid explants were employed and intravitreal injections were performed in animals.
  
  
  RESULTS
  The authors herein demonstrate that deficient vascularity occurs not only in the retinal plexus but also in the choroid. This sustained, marked choroidal degeneration is specifically confined to central regions of the retina that present persistent photoreceptor loss and corresponding functional deficits. Moreover, the authors show that 15d-PGJ(2) is a prominent contributor to this choroidal decay.
  
  
  CONCLUSIONS
  The authors demonstrate for the first time pronounced, sustained choroidal vascular involution during the development of ROP. Findings also suggest that effective therapeutic strategies to counter ROP should consider choroidal preservation.
authors.affiliation: Department of Ophthalmology and Pharmacology, Hôpital Sainte-Justine Research Center, Montreal, Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Shao
authors.forename: Allison L
authors.initials: AL
authors.lastname: Dorfman
authors.forename: Swathi
authors.initials: S
authors.lastname: Seshadri
authors.forename: Mikheil
authors.initials: M
authors.lastname: Djavari
authors.forename: Elsa
authors.initials: E
authors.lastname: Kermorvant-Duchemin
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.forename: Martine
authors.initials: M
authors.lastname: Blais
authors.forename: Anna
authors.initials: A
authors.lastname: Polosa
authors.forename: Daya R
authors.initials: DR
authors.lastname: Varma
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Joyal
authors.forename: Pierre
authors.initials: P
authors.lastname: Lachapelle
authors.forename: Pierre
authors.initials: P
authors.lastname: Hardy
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sitaras
authors.forename: Emilie
authors.initials: E
authors.lastname: Picard
authors.forename: Joseph
authors.initials: J
authors.lastname: Mancini
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002829:Choroid / Q000098:blood supply*; D015862:Choroid Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016319:Corrosion Casting; D004195:Disease Models, Animal; D004596:Electroretinography; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D055254:Night Vision; D010100:Oxygen / Q000633:toxicity; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C477819:15-deoxyprostaglandin J2; D015230:Prostaglandin D2; D010100:Oxygen