Deakin University, School of Medicine, Faculty of Health, 75 Pigdons Road, Waurn Ponds, Geelong, VIC, 3216, Australia.
Monash University, Australian Regenerative Medicine Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia.
Sci Rep. 2019 Mar 11;9(1):4121. doi: 10.1038/s41598-019-41009-3.
Maternal hyperglycaemia has a profound impact on the developing foetus and increases the risk of developing abnormalities like obesity, impaired glucose tolerance and insulin secretory defects in the post-natal life. Increased levels of glucose in the blood stream due to diabetes causes visual disorders like retinopathy. However, the impact of maternal hyperglycaemia due to pre-existing or gestational diabetes on the developing foetal retina is unknown. The aim of this work was to study the effect of hyperglycaemia on the developing retina using zebrafish as a vertebrate model. Wild-type and transgenic zebrafish embryos were exposed to 0, 4 and 5% D-Glucose in a pulsatile manner to mimic the fluctuations in glycaemia experienced by the developing foetus in pregnant women with diabetes. The zebrafish embryos displayed numerous ocular defects associated with altered retinal cell layer thickness, increased presence of macrophages, and decreased number of Müeller glial and retinal ganglion cells following high-glucose exposure. We have developed a model of gestational hyperglycaemia using the zebrafish embryo to study the effect of hyperglycaemia on the developing embryonic retina. The data suggests that glucose exposure is detrimental to the development of embryonic retina and the legacy of this exposure may extend into adulthood. These data suggest merit in retinal assessment in infants born to mothers with pre-existing and gestational diabetes both in early and adult life.
母体高血糖对发育中的胎儿有深远的影响,并增加了在出生后生活中发展异常的风险,如肥胖、葡萄糖耐量受损和胰岛素分泌缺陷。由于糖尿病导致血液中葡萄糖水平升高,会引起视网膜病变等视觉障碍。然而,由于先前存在的或妊娠糖尿病引起的母体高血糖对发育中的胎儿视网膜的影响尚不清楚。这项工作的目的是使用斑马鱼作为脊椎动物模型来研究高血糖对发育中视网膜的影响。野生型和转基因斑马鱼胚胎以脉冲方式暴露于 0、4 和 5%的 D-葡萄糖中,以模拟糖尿病孕妇中胎儿经历的血糖波动。高葡萄糖暴露后,斑马鱼胚胎表现出许多与视网膜细胞层厚度改变、巨噬细胞增多以及 Müller 胶质细胞和视网膜神经节细胞减少相关的眼部缺陷。我们使用斑马鱼胚胎开发了一种妊娠高血糖模型,以研究高血糖对发育中胚胎视网膜的影响。数据表明,葡萄糖暴露对胚胎视网膜的发育有害,这种暴露的后果可能会延续到成年期。这些数据表明,对于患有先前存在的和妊娠糖尿病的母亲所生的婴儿,在早期和成年生活中都需要进行视网膜评估。