Abnormal retinal function after oxygen-induced retinopathy under maternal hyperglycemic condition

Abstract

Purpose: Maternal diabetes is associated with retinopathy of prematurity (ROP). The influence of maternal diabetes on ROP progression and severity is investigated in retina of pups from hyperglycemic C57Bl/6 Ins2Akita/J (Akita) mothers subjected to oxygen-induced retinopathy (OIR). Methods: Genotyping and blood glucose measurement of Akita mice were performed before 10 weeks of age. The pups and their nursing mother were placed into a chamber with 75% oxygen from postnatal day (P)7 to P12 and subsequently returned to room air. Pups from C57Bl/6J (wildtype, WT) or Akita mothers were sacrificed on P7, 12, 17, 21, and 30. The retinal vascular network was visualized using isolectin B4 immunostaining and retinal function was assessed by electroretinography (ERG). Results: Hyperglycemia was well-developed in 10-week-old Akita mothers. They displayed higher pregnancy risks including dystocia and higher mortality rate of pups. The pups from Akita mothers were heavier after 21-day-old but had larger weight loss after OIR. Under room air condition, the pups from either WT or Akita mothers displayed normal retinal vascular and functional development. After OIR, despite a similar extent of avascularization, pups from Akita mothers had smaller neovascular area on P21. The a-wave and b-wave amplitudes were reduced significantly after OIR in both groups, but the pups from Akita mothers had a slower recovery rate in a-wave amplitude. Conclusions: Normal retinal vascular and functional development were not affected by maternal hyperglycemia. However, the retinal function of neonates from hyperglycemic mothers was disrupted by OIR and showed a slower recovery rate, suggesting a sustained deficit in photoreceptor functions.