title: Early Postnatal Hyperoxia in Mice Leads to Severe Persistent Vitreoretinopathy.
abstract: To describe a mouse model of hyperoxia-induced vitreoretinopathy that replicated some of the clinical and pathologic features encountered in infants with severe retinopathy of prematurity and congenital ocular conditions such as persistent hyperplastic primary vitreous.
  
  
  
  Experimental mice (C57BL/6J) were exposed to 65% oxygen between postnatal days (P)0 to P7 and studied at P10, P14, and 3, 5, 8, 20, and 40 weeks. Controls were exposed to normoxic conditions. Fundus imaging and fluorescein angiography were performed at all time points, and spectral-domain optical coherence tomography (SD-OCT) and electroretinography were performed at 8- and 20-week time points. Eyes were processed for resin histology, frozen sections, and retinal whole mounts. Immunostaining was performed to visualize vasculature isolectin B4 (Ib4), collagen type IV, glial fibrillary acidic protein, and α-smooth muscle actin.
  
  
  
  Early exposure to hyperoxia resulted in bilateral vitreous hemorrhages at 3 weeks. From 5 weeks onward there were extensive zones of retinal degeneration, scarring or gliosis, retinal folding, and detachments caused by traction of α-smooth muscle actin-positive vitreous membranes. Tortuous retinal vessels, together with hyperplastic and persistence of hyaloid vessels are evident into adulthood. In the early stages (P10-3 weeks), branches from the tunica vasculosa lentis (TVL) supplied the marginal retina until retinal vessels were established. The peripheral retina remained poorly vascularized into adulthood. Electroretinography revealed 50% to 60% diminution in retinal function in adult mice that strongly correlated with vitreal changes identified using SD-OCT.
  
  
  
  This animal model displays a mixture of vitreoretinal pathologic changes that persist into adulthood. The model may prove valuable in experimental investigations of therapeutic approaches to blinding conditions caused by vitreous and retinal abnormalities.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kenny
authors.affiliation: Klinik Mata Nusantara, Jakarta, Indonesia.
authors.forename: Sjakon
authors.initials: S
authors.lastname: Tahija
authors.affiliation: Department of Optometry and Vision Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Naranjo Golborne
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Sheena
authors.initials: S
authors.lastname: Bouch
authors.affiliation: Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Foula
authors.initials: F
authors.lastname: Sozo
authors.affiliation: Department of Optometry and Vision Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Bang
authors.initials: B
authors.lastname: Bui
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D018496:Hyperoxia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism*; D012171:Retinal Vessels / Q000473:pathology* / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D010100:Oxygen