Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Program in Biology, Rhodes College, Memphis, TN 38112, USA.
Int J Mol Sci. 2022 Aug 26;23(17):9693. doi: 10.3390/ijms23179693.
Embryonic hyperglycemia negatively impacts retinal development, leading to abnormal visual behavior, altered timing of retinal progenitor differentiation, decreased numbers of retinal ganglion cells and Müller glia, and vascular leakage. Because synaptic disorganization is a prominent feature of many neurological diseases, the goal of the current work was to study the potential impact of hyperglycemia on retinal ribbon synapses during embryonic development. Our approach utilized reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence labeling to compare the transcription of synaptic proteins and their localization in hyperglycemic zebrafish embryos, respectively. Our data revealed that the maturity of synaptic ribbons was compromised in hyperglycemic zebrafish larvae, where altered expression coincided with the delay in establishing retinal ribbon synapses and an increase in the immature synaptic ribbons. Our results suggested that embryonic hyperglycemia disrupts retinal synapses by altering the development of the synaptic ribbon, which can lead to visual defects. Future studies using zebrafish models of hyperglycemia will allow us to study the underlying mechanisms of retinal synapse development.
胚胎高血糖会对视网膜发育产生负面影响，导致异常的视觉行为、视网膜祖细胞分化时间改变、视网膜神经节细胞和 Muller 胶质细胞数量减少以及血管渗漏。由于突触紊乱是许多神经疾病的一个突出特征，因此当前工作的目标是研究胚胎发育过程中高血糖对视网膜带状突触的潜在影响。我们的方法分别利用逆转录定量 PCR（RT-qPCR）和免疫荧光标记来比较突触蛋白的转录和它们在高血糖斑马鱼胚胎中的定位。我们的数据表明，在高血糖斑马鱼幼虫中，突触带的成熟受到了损害，其中改变的表达与视网膜带状突触建立的延迟以及未成熟的突触带增加相吻合。我们的结果表明，胚胎高血糖通过改变突触带的发育而破坏视网膜突触，从而导致视觉缺陷。使用高血糖斑马鱼模型的未来研究将使我们能够研究视网膜突触发育的潜在机制。
