Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Center for Visual Science, University of Rochester, Rochester, NewYork, USA.
Sci Rep. 2018 Jan 18;8(1):1096. doi: 10.1038/s41598-018-19425-8.
To discover the mechanisms underlying the progression of diabetic retinopathy (DR), a more comprehensive understanding of the biomolecular processes in individual retinal cells subjected to hyperglycemia is required. Despite extensive studies, the changes in the biochemistry of retinal layers during the development of DR are not well known. In this study, we aimed to determine a more detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes model) male mice with different duration of diabetes. Employing label-free spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged with multivariate analysis enabled us to identify temporal-dependent reproducible biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6 months, and 10 months of age. We report, for the first time, the nature of the biochemical alterations over time in the biochemistry of distinctive retinal layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and plexiform layers (OPL, IPL). Moreover, we present the molecular factors associated with the changes in the protein structure and cellular lipids of retinal layers induced by different duration of diabetes. Our paradigm provides a new conceptual framework for a better understanding of the temporal cellular changes underlying the progression of DR.
为了揭示糖尿病性视网膜病变（DR）进展的机制，需要更全面地了解高血糖状态下个体视网膜细胞中的生物分子过程。尽管已经进行了广泛的研究，但 DR 发展过程中视网膜各层的生化变化仍知之甚少。在这项研究中，我们旨在通过不同病程的 Akita/+（1 型糖尿病模型）雄性小鼠，更详细地了解 DR 的自然史。采用无标记空间分辨傅里叶变换红外（FT-IR）化学成像结合多变量分析，我们能够从 6 周、12 周、6 个月和 10 个月大的小鼠中确定各个视网膜层的具有时间依赖性的、可重复的生物标志物。我们首次报告了随时间推移，在特有的视网膜层（感光器视网膜层 [PRL]、内核层 [INL] 和神经纤维层 [OPL、IPL]）的生化中出现的生化改变的本质。此外，我们还介绍了与不同病程糖尿病引起的视网膜层的蛋白质结构和细胞脂质变化相关的分子因素。我们的研究范式为更好地理解 DR 进展背后的时空细胞变化提供了新的概念框架。
