Effect Of Premature Birth On Retinal Development In The Neonatal Rat

BACKGROUNDPreterm birth is a common clinical phenomenon which can be caused by severalfactors. Premature infants’ vision system that is in the sensitively developing stages couldbe exposed to the external environment and their Ω-3fatty acid which is obtained frommother and is accosiated with the development of vision system could be deprivedbecause they break away from the environment of uterus ahead of time. So the prematurebirth turns to be a high risk factor of abnormal development in the morphology andfunction of vision system and a high risk factor of eye diseases. Compared with terminfants, the ocular morphology of early stage and the visual funcion of later stage ofpreterm infants have specific characteristics while the visual damage and the abnormalocular development are more common. For example, the morbidity of ROP is obviouslyincreased in preterm infants. ROP is a complex vasoproliferative disorder characterized asdevelopment of abnormal retinal vasculature in preterm infants, which have lowgestational age or low birth weight, its etiology is complex and pathological mechanism isnot clear.Oxygen-induced retinopathy (OIR) rat model is widely used in experimental research on ROP based on the fact of immature retinal vasculature of the neonatal. However, thegeneral condition of newborn rat with normal parturition in OIR is different frompathophysiological conditions of newborn preterm infants. The situation of growth anddevelopment during antenatal and postnatal periods have a decisive role in abnormalneovascularization of ROP. Theoretically, premature animals could better simulate theclinical preterm children born with an immature state and stunted experience. Based onthis, this study aims to observe the effect of premature birth on the structural andfunctional development of neonatal rat retina vasculature and laying the foundation forsubsequent research.PURPOESTo investigate the effect of premature birth on the structural and functionaldevelopment of neonatal rat retina, laying the foundation for subsequent research in ROP.METHODS1. Newborn Sprague-Dawley (SD) rats were delivered prematurely at day19ofgestation by caesarean section、 intraperitoneal injection of LPS and Subcutaneousinjection of RU-486from pregnant female rats. General state and weight change wereobserved. Naturally delivered term pups were used as control;2. On postnatal day4、7、10and14(P4、P7、P10and P14), cross-sections of retinawere stained with hematoxylin and eosin (H&E) for histopathological examination;3. On postnatal day4、7、10and14(P4、P7、P10and P14), retina were dissected，whole-mounted and stained using Isolectin B4for morphology observation;4. On postnatal day14、21and28(P14、P21and P28), electroretinogram (ERG) wasperformed on pups and the amplitude and implicit time of the waves were recorded.RESULTS1. Preterm birth was induced successfully by three methods with high survival rate ofneonatal rat pups. Preterm rat pups had lower body weight than control group within thefirst3weeks after birth (P＜0.05);2. The morphology of retinal cells was similar in the four groups. On P4and P7, the number of neuroblast layers was more than the control group in these three pretermgroups，with a significant differences between them (P＜0.05); On P10and P14, thenumber of outer nuclear cell layers and internal nuclear layer in the four group was similar,with no differences between them;3. The morphology of retinal superficial vessels was similar in the four groups. OnP4and P7of LPS group, the proportion of retinal superficial vascularized area of newbornratswas less than the control group (P＜0.05); On P4and P7of RP group，this proportionwas less than the control group (P＜0.05); On P4, P7and P10of CP group, thisproportionwas less than the control group (P＜0.05);4. Functionally, the amplitude and latency of ERG waves were similar in the fourgroups. On P14in LP group, the implicit time of Max-a wave and Max-b wave was longerthan that in the control group; In CP group, the implicit time of Rod-b wave、Max-b waveand Cone-b wave were longer than that of the control group; In RP group, the implicittime of Max-b wave was longer than that of the control group; On P21in LP group, theimplicit time of Max-a wave and Max-b wave were longer than that of the control group;On P28in LP group, the implicit time of Max-b wave was longer than that of the controlgroup (P＜0.05).CONCLUSIONSPreterm birth induced by caesarean section intraperitoneal injection of LPS andSubcutaneous injection of RU-486had obvious negative effect on the body growth as wellas the neuroretinal and retinal vascular development of the neonatal rats. The developmentof retinal structure and function is slower in preterm rats than that in normal ones, whichmay be the anatomical basis in elucidation of complex mechanisms of ROP.