title: Altered retinal function and structure after chronic placental insufficiency.
abstract: OBJECTIVE
  To consider whether growth restriction secondary to chronic placental insufficiency results in postnatal deficits in retinal structure and function.
  
  
  METHODS
  Chronic placental insufficiency was induced just before midgestation in guinea pigs through unilateral ligation of the uterine artery. Eight weeks after birth, electroretinograms were recorded from prenatally compromised (PC, n = 6) and control (n = 15) animals. Data were collected for b-wave amplitude and implicit time, also the modeled receptoral (P3) response and oscillatory potentials were extracted. After electroretinography, retinas were prepared for structural analysis (PC, n = 6; control, n = 7). A separate cohort of PC (n = 8) and control (n = 9) animals underwent tyrosine hydroxylase immunoreactivity (TH-IR, dopaminergic neurons) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry (neuronal nitric oxide synthase, nNOS)--these being markers of amacrine cell subpopulations.
  
  
  RESULTS
  Electroretinography revealed two PC guinea pigs with marked changes to saturated receptoral amplitude (Rm(P3)), sensitivity (log S) and postreceptoral waveforms. Grouped PC data revealed significantly reduced Rm(P3), whereas log S was not affected. The b-wave amplitudes were normal, but b-wave implicit times were delayed (P < 0.05) in PC animals. Amplitudes and peak times of oscillatory potentials were also significantly reduced and delayed (P < 0.05). Morphologic analysis revealed significant reductions in all cellular and plexiform (synaptic) layers in both the central (P < 0.05) and peripheral (P < 0.05) retina in PC animals. The outer retina, which contains the photoreceptors and the outer plexiform layer was particularly affected. The reduced growth of plexiform layers suggests a reduction in the growth of the neuropile in PC animals compared with control animals. The total number (P < 0.03) and density (P < 0.05) of TH-IR neurons was reduced, whereas the total number and density of nNOS-positive amacrine cells was not significantly different between PC and control animals.
  
  
  CONCLUSIONS
  Chronic placental insufficiency results in morphologic and functional alterations to the retina. Electroretinogram deficits in PC animals indicated both inner and outer retinal anomalies. Such affects could contribute to the visual impairments reported in very-low-birth-weight children, some of whom are growth restricted.
authors.affiliation: Department of Optometry and Vision Sciences, University of Melbourne 3010, Carlton, Victoria 3053, Australia.
authors.forename: Bang V
authors.initials: BV
authors.lastname: Bui
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Rees
authors.forename: Michelle
authors.initials: M
authors.lastname: Loeliger
authors.forename: Jacinta
authors.initials: J
authors.lastname: Caddy
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Rehn
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.forename: Algis J
authors.initials: AJ
authors.lastname: Vingrys
mesh_terms: D025042:Amacrine Cells / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D004596:Electroretinography; D005260:Female; D006168:Guinea Pigs; D007124:Immunoenzyme Techniques; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010927:Placental Insufficiency / Q000150:complications / Q000503:physiopathology*; D011247:Pregnancy; D012160:Retina / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D012164:Retinal Diseases / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014786:Vision Disorders / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*
chemical_list: D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D009252:NADPH Dehydrogenase