Retinal function, retinal vasculature and physical development were more severely affected in pups from hyperglycemia mice after oxygen-induced retinopathy

Abstract

Purpose: Maternal diabetes was recently identified as an independent risk factor for retinopathy of prematurity (ROP). To investigate the effect of maternal diabetes on ROP in body weight and retinal development, a hyperglycemic Ins2Akita/+ (Akita) mouse oxygen-induced retinopathy (OIR) model was used. Methods: Pups with their wildtype (WT) or Akita mothers received 75% oxygen from postnatal (P) day 7 to 12. They were then returned to room air (RA). Pregnancy risks of mothers were recorded. At P7, 12, 17, 21, and 30, body weight of pups was measured. Retinal function was assessed using scotopic electroretinography (ERG) at P17, 21 and 30. To examine the retinal vascular changes after OIR, retinal whole mounts were collected and stained with isolectin B4 (GS-IB4) by immunohistochemistry. Results: We observed that Akita mothers have higher pregnancy risks, including higher dystocia rate (WT: 6.1%, Akita: 12.7%) and number of dead pups from the same litter (WT: 10.1%, Akita: 16.3%). Under normal condition, increase in body weight of pups from Akita mothers was higher than those form WT mothers over the period from P12 to P30. Meanwhile, more significant drop in body weight after OIR was observed in pups from Akita mothers throughout the study (P21: p<0.001, P30: p<0.01). We further analyzed the retinal vasculature and retinal function of these pups. Normal vasculature was observed in isolectin-stained retinal flat mounts under RA condition. Similar to the pups from WT mothers, central avascular zone and neovascular tufts were induced in the pups from Akita mothers. There was no significant difference in the size of the avascular area. However, fewer neovascular tufts were observed in the pups from Akita mothers at P21 comparing with WT (p<0.05). For retinal function analysis, there was no significant difference in a- and b-wave amplitudes between the pups from WT and Akita mothers under RA or OIR. More importantly, the pups from Akita mothers have a slower recovery rate in a-wave amplitude from P17 to 30 after OIR. Conclusions: More severe body weight loss and slower recovery rate in a-wave amplitude were observed in the pups from Akita mothers, suggesting that physical development and photoreceptor function were more susceptible in the pups from hyperglycemic mothers after OIR.