Postnatal growth retardation exacerbates acidosis-induced retinopathy in the neonatal rat.
OBJECTIVE
We have previously described a metabolic acidosis-induced retinopathy in the neonatal rat, similar to retinopathy of prematurity (ROP). We also have reported exacerbation of oxygen-induced retinopathy by postnatal growth retardation, produced by raising newborn rats in 'expanded' litters. In the present study, we investigated the effect of postnatal growth retardation on the incidence and severity of acidosis-induced retinopathy.


METHODS
100 newborn Sprague-Dawley rats were randomly assigned to two expanded litters of 25 pups each and five standard control litters of 10 pups each. All rats were gavaged with 10 mM/kg NH(4)Cl twice daily from days two to seven. Following five days of recovery, retinal vasculature was assessed using ADPase staining, light microscopy, and computer-assisted image analysis. The presence of neovascularization (NV), severity of NV (clock hours), and vascularized retinal areas, were evaluated in a masked manner.


RESULTS
NV occurred in 52% of rats in expanded litters versus 18% of rats in standard control litters (p = 0.005). Postnatal growth retardation of pups in expanded litters was confirmed by comparing total body weight of pups raised in expanded and standard control litters (10.8g vs 13.4g on day 8, p < 0.001; 20.8g vs 25.2g on day 13, p = 0.002).


CONCLUSIONS
Postnatal growth retardation increases the incidence of acidosis-induced retinopathy in the neonatal rat. Our study provides further evidence that postnatal growth retardation is a risk factor for preretinal neovascularization in immature retinae and is consistent with the clinical observation that the smallest and sickest premature infants are more likely to suffer from ROP.
Zhang
S
S
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Leske
D A
DA
Lanier
W L
WL
Holmes
J M
JM
D000138:Acidosis / Q000209:etiology*; D000643:Ammonium Chloride / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001081:Apyrase / Q000378:metabolism; D001784:Blood Gas Analysis; D001835:Body Weight; D006130:Growth Disorders / Q000150:complications*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D008098:Litter Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012171:Retinal Vessels / Q000201:enzymology / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012307:Risk Factors
D000643:Ammonium Chloride; D001081:Apyrase