title: Prenatal hypoxia is associated with long-term retinal dysfunction in rats.
abstract: BACKGROUND
  Intra-uterine growth restriction (IUGR) has been associated with increased predisposition to age-related complications. We tested the hypothesis that rat offspring models of IUGR would exhibit exacerbated, age-related retinal dysfunction.
  
  
  METHODS
  Female Sprague-Dawley rats (maintained at 11.5% O2 from gestational day 15 to 21 to induce IUGR) and control offspring (maintained at 21% O2 throughout pregnancy) had retinal function assessed at 2 months (young) and 14 months of age (aged) with electroretinogram (ERG) recordings. Retinal anatomy was assessed by immunofluorescence.
  
  
  RESULTS
  Deficits in rod-driven retina function were observed in aged IUGR offspring, as evidenced by reduced amplitudes of dark-adapted mixed a-wave V(max) (by 49.3%, P < 0.01), b-wave V(max) (by 42.1%, P < 0.001) and dark-adapted peak oscillatory potentials (by 42.3%, P < 0.01). In contrast to the rod-driven defects specific to aged IUGR offspring, light adapted ERG recordings revealed cone defects in young animals, that were stationary until old age. At 2 months, IUGR offspring had amplitude reductions for both b-wave (V(max) by 46%, P < 0.01) and peak oscillatory potential (V(max) by 38%, P < 0.05). Finally, defects in cone-driven responses were further confirmed by reduced maximal photopic flicker amplitudes at 2 (by 42%, P < 0.001) and 14 months (by 34%, P  =  0.06) and critical flicker fusion frequencies at 14 months (
  
  
  METHODS
  42 ± 1 Hz, IUGR: 35 ± 2 Hz, P < 0.05). These functional changes were not paralleled by anatomical losses in IUGR offspring retinas.
  
  
  CONCLUSIONS
  These data support that the developing retina is sensitive to stressors, and that pathways governing cone- and rod-driven function differ in their susceptibilities. In the case of prenatal hypoxia, cone- and rod-driven dysfunction manifest at young and old ages, respectively. We must, therefore, take into account the specific impact that fetal programming might exert on age-related retinal dystrophies when considering related diagnoses and therapeutic applications.
authors.affiliation: Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Stephane L
authors.initials: SL
authors.lastname: Bourque
authors.forename: Sharee
authors.initials: S
authors.lastname: Kuny
authors.forename: Laura M
authors.initials: LM
authors.lastname: Reyes
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Yves
authors.initials: Y
authors.lastname: Sauvé
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects; D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D003624:Darkness; D005260:Female; D000860:Hypoxia / Q000196:embryology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000196:embryology / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology / Q000502:physiology / Q000528:radiation effects