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The effect of postnatal growth retardation on abnormal neovascularization in the oxygen exposed neonatal rat
1Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA.
Insights
Larger litters in premature infants lead to growth retardation, increasing the risk and severity of retinopathy of prematurity (ROP). This study shows growth-restricted rat pups develop more abnormal retinal neovascularization.
Area of Science:
- Ophthalmology
- Neonatology
- Developmental Biology
Background:
- Severe retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants.
- ROP is characterized by abnormal blood vessel growth in the retina.
- Postnatal growth retardation is a known risk factor for ROP.
Purpose of the Study:
- To investigate the relationship between litter size, postnatal growth retardation, and the development of abnormal retinal neovascularization in a rat model.
- To determine if increased litter size, leading to growth restriction, exacerbates oxygen-induced retinopathy.
Main Methods:
- Newborn Sprague-Dawley rats were divided into large (n=25) and small (n=10) litters.
- Litters were exposed to cyclic hyperoxia and hypoxia, followed by room air.
- Retinal neovascularization was assessed using ADPase staining and quantified via digital image analysis of fluorescein-perfused retinae.
Main Results:
- Rats in larger litters had significantly lower final weights compared to those in smaller litters.
- Neovascularization occurred more frequently (53% vs. 15%) and was more severe in rats from larger litters.
- Smaller body weight was correlated with increased severity of retinal neovascularization.
Conclusions:
- Postnatal growth retardation, induced by larger litter sizes, increases the incidence and severity of abnormal retinal neovascularization.
- These findings in a rat model support the clinical observation that growth-restricted premature infants are at higher risk for severe ROP.
Abstract:
Severe retinopathy of prematurity (ROP) occurs in the smallest and sickest of premature infants. We hypothesized that, in a rat model of oxygen induced retinopathy, abnormal neovascularization would occur more frequently in larger litters where the pups are subject to postnatal growth retardation. Four litters of newborn Sprague-Dawley rats were studied; rats were randomly mixed to form two large litters (n = 25 each) and two small litters (n = 10 each). All litters were exposed to 7 days cyclic hyperoxia and hypoxia followed by 5 days in room air. ADPase stained retinae were evaluated in a masked manner for the presence and severity of abnormal neovascularization. Fluorescein perfused retinae were digitized and the ratios of vascularized:total retinal area were calculated using computer assisted image analysis. As expected, final weight in the large litters was less than in the small litters (15.3 +/- 3.8g vs. 23.4 +/- 2.1g, p < 0.001). Neovascularization occurred in 53% of rats in the large litters vs. 15% in the small litters (p = 0.009). Rats with retinae demonstrating neovascularization were smaller than those without (16.2 +/- 4.7g vs. 19.6 +/- 5.0g, p = 0.016). The severity of neovascularization in clock h was inversely correlated with final weight (rs = -0.35, p = 0.01) and ratio of vascularized:total retina area (rs = -0.46, p < 0.001). Smaller rat pups raised in larger litters, with resultant growth retardation, develop more frequent and more severe abnormal retinal neovascularization. Our results correlate with clinical experience in the premature infant.