title: Incidence and severity of neovascularization in oxygen- and metabolic acidosis-induced retinopathy depend on rat source.
abstract: OBJECTIVE
  We have previously described oxygen-induced retinopathy (OIR) and metabolic acidosis-induced retinopathy (MAIR) in the neonatal rat, both of which are analogous to human retinopathy of prematurity (ROP). Given that rats of identical strain from two commercial suppliers are phenotypically different, we investigated the incidence and severity of preretinal neovascularization (NV) in rats from different suppliers using the OIR and MAIR models.
  
  
  METHODS
  Using our established models for OIR and MAIR, 400 newborn Sprague-Dawley rats, obtained from Harlan Laboratories (HSD) and Charles River Laboratories (CRSD), were raised in 16 expanded litters of 25 (6 OIR and 10 MAIR). Beginning at day 1 of life, OIR litters (3 HSD, 3 CRSD) were exposed to 7 daily cycles of hyperoxia (80% O(2), 20.5 hours) and hypoxia (10% O(2), 0.5 hours) with a gradual return to 80% O(2) over 3 hours. OIR rats were sacrificed after 5 days of room air recovery. MAIR litters (5 HSD, 5 CRSD) were raised in room air and gavaged twice daily with NH(4)Cl (10 mM/kg body weight) from day 2 through day 4. MAIR rats were sacrificed after 3 days of recovery. For both OIR and MAIR litters, retinae from left eyes were dissected, ADPase-stained, and flatmounted. Presence and severity of NV was scored and retinal vascular areas measured by a masked observer.
  
  
  RESULTS
  In OIR rats, the incidence of NV was higher in CRSD rats than HSD rats (73% vs. 45%, p = 0.002). NV was more severe in CRSD rats than HSD rats (median clock hours 2 vs. 0, p = 0.0001). In MAIR rats, the incidence of NV was comparable between CRSD and HSD rats (29% vs. 34%, p = 0.53) and there was no significant difference in the severity of NV.
  
  
  CONCLUSIONS
  Sprague-Dawley rats obtained from two independent commercial sources differed in their incidence and severity of NV associated with OIR, but not with MAIR. Future genetic studies are warranted to investigate the differences between CRSD and HSD rats, which might yield further clues into the pathogenesis of ROP.
authors.affiliation: Mayo Medical School, Rochester, MN 55905, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Kitzmann
authors.forename: David
authors.initials: D
authors.lastname: Leske
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Andrea
authors.initials: A
authors.lastname: Kendall
authors.forename: William
authors.initials: W
authors.lastname: Lanier
authors.forename: Jonathan
authors.initials: J
authors.lastname: Holmes
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000150:complications*; D000375:Aging; D000643:Ammonium Chloride / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008098:Litter Size / Q000187:drug effects / Q000502:physiology; D010100:Oxygen; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000453:epidemiology / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D013045:Species Specificity
chemical_list: D000643:Ammonium Chloride; D010100:Oxygen