Effect of IGF-1 Administration on Retinopathy in a Low-Birth-Weight Rat Model of Oxygen-Induced Retinopathy

Abstract

Purpose : Long-term low levels of serum Insulin-like growth factor-1 (IGF-1) in premature infants have been reported to increase the risk of retinopathy of prematurity and maintaining high serum IGF-1 levels early in life in premature infants may be a way to prevent postnatal complications.
We previously reported a small for gestational age model (SGA-rat) in which pregnant rats were fed a protein-restricted diet to induce intrauterine growth failure of the fetuses and were born with low birth weight (Saito et al. 2014 ARVO). Serum IGF-1 in SGA-rats at day 8 (P8) was significantly lower than that in rats born to pregnant rats fed a normal diet. In this study, we investigated the effect of IGF-1 administration on SGA-rats of Oxygen-Induced Retinopathy (OIR).

Methods : Pregnant Sprague-Dawley rats were purchased and fed a normal diet (20% protein) (control group: Cnt-rat) or a low-protein diet (10% protein) (SGA-rat) with equivalent calories from day 13 of gestation. For OIR, OxyCycler was used for oxygen loading for 7 cycles (from birth to P14) with 50% O₂/24h and then 10% O₂/24h as one cycle, and the rats were kept in ambient air until P18.
Experiment 1: After weighing the pups at P18, the blood was collected from the heart, and the removed right eye was fixed to prepare retinal flatmounts. From these retinal flatmounts, we assessed the severity of retinopathy (Clock Hours: CH) and measured the percentage of avascular area to total retinal area (%AVA). In the left eye, the retina was homogenized and measured the intraretinal vascular endothelial growth factor (VEGF) and IGF-1 concentrations by ELISA. Serum IGF-1 concentration was also measured by ELISA, and the endpoints were compared between SGA-rat and Cnt-rat.
Experiment 2: To exogenously supplement IGF-1 to SGA-rat, IGF-1 (2ug/g body weight) was subcutaneously administered once daily from P4 to P14 (SGA-IGF1-rat), and the same endpoints as in Experiment 1 at P14 and P18 were compared with the control group (SGA-PBS-rat) that received PBS.
The results obtained are presented as mean ± standard deviation, and statistical analysis was performed using Wilcoxon test with p-value < 0.05 as significant difference.

Results : The results are shown in Table 1.

Conclusions : In SGA-rat, low IGF-1 levels immediately after birth did not contribute to the worsening of retinopathy, but rather IGF-1 administration worsened retinopathy.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.