Özgümüs Türküler, Sulaieva Oksana, Jain Ruchi, Artner Isabella, Lyssenko Valeriya
Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.
Medical Laboratory CSD, Kyiv, Ukraine.
Front Cell Dev Biol. 2021 Nov 18;9:726852. doi: 10.3389/fcell.2021.726852. eCollection 2021.
Perinatal exposure to starvation is a risk factor for development of severe retinopathy in adult patients with diabetes. However, the underlying mechanisms are not completely understood. In the present study, we shed light on molecular consequences of exposure to short-time glucose starvation on the transcriptome profile of mouse embryonic retinal cells. We found a profound downregulation of genes regulating development of retinal neurons, which was accompanied by reduced expression of genes encoding for glycolytic enzymes and glutamatergic signaling. At the same time, glial and vascular markers were upregulated, mimicking the diabetes-associated increase of angiogenesis-a hallmark of pathogenic features in diabetic retinopathy. Energy deprivation as a consequence of starvation to glucose seems to be compensated by upregulation of genes involved in fatty acid elongation. Results from the present study demonstrate that short-term glucose deprivation during early fetal life differentially alters expression of metabolism- and function-related genes and could have detrimental and lasting effects on gene expression in the retinal neurons, glial cells, and vascular elements and thus potentially disrupting gene regulatory networks essential for the formation of the retinal neurovascular unit. Abnormal developmental programming during retinogenesis may serve as a trigger of reactive gliosis, accelerated neurodegeneration, and increased vascularization, which may promote development of severe retinopathy in patients with diabetes later in life.
围产期饥饿暴露是成年糖尿病患者发生严重视网膜病变的一个危险因素。然而，其潜在机制尚未完全明确。在本研究中，我们揭示了短期葡萄糖饥饿暴露对小鼠胚胎视网膜细胞转录组谱的分子影响。我们发现，调节视网膜神经元发育的基因显著下调，同时糖酵解酶和谷氨酸能信号相关基因的表达也降低。与此同时，胶质细胞和血管标志物上调，模拟了糖尿病相关的血管生成增加——这是糖尿病视网膜病变致病特征的一个标志。葡萄糖饥饿导致的能量剥夺似乎通过上调参与脂肪酸延长的基因来代偿。本研究结果表明，胎儿早期的短期葡萄糖剥夺会差异性地改变代谢和功能相关基因的表达，并可能对视网膜神经元、胶质细胞的基因表达产生有害和持久的影响，从而潜在地破坏视网膜神经血管单元形成所必需的基因调控网络。视网膜生成过程中的异常发育编程可能引发反应性胶质增生、加速神经退行性变以及增加血管生成，这可能促进糖尿病患者后期严重视网膜病变的发展。
