TY - JOUR
T1 - Incidence and severity of neovascularization in oxygen- and metabolic acidosis-induced retinopathy depend on rat source
AU - Kitzmann, Anna S.
AU - Leske, David A.
AU - Chen, Yi
AU - Kendall, Andrea M.
AU - Lanier, William L.
AU - Holmes, Jonathan M.
N1 - Funding Information:
This study was supported by a National Institutes of Health Grant EY12798 (JMH), Research to Prevent Blindness, Inc., New York, New York (JMH as RPB Olga Keith Weiss Scholar and an unrestricted grant to the Department of Ophthalmology, Mayo Clinic), the Mayo Foundation, Rochester, Minnesota, and the philanthropy of Margaret Schroeder (JMH).
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Purpose. 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% O2, 20.5 hours) and hypoxia (10% O2, 0.5 hours) with a gradual return to 80% O2 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 NH4Cl (10mM/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.
AB - Purpose. 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% O2, 20.5 hours) and hypoxia (10% O2, 0.5 hours) with a gradual return to 80% O2 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 NH4Cl (10mM/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.
KW - Animal model
KW - Rat
KW - Retinal neovascularization
KW - Retinopathy of prematurity
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U2 - 10.1076/ceyr.25.4.215.13483
DO - 10.1076/ceyr.25.4.215.13483
M3 - Article
C2 - 12658554
AN - SCOPUS:0036820720
SN - 0271-3683
VL - 25
SP - 215
EP - 220
JO - Current Eye Research
JF - Current Eye Research
IS - 4
ER -