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Responses of retinal and brain microvasculature to streptozotocin induced diabetes revealed by global expression profiling.

ABSTRACT: This study aims to determine the effects of diabetes in the retinal and brain microvasculature through gene expression profiling. Twelve male Wistar rats were randomly divided into two groups: streptozotocin-induced diabetic rats and time-matched nondiabetic rats. The retinal microvessels (RMVs) and brain microvessels (BMVs) were mechanically isolated from individual rats. Differentially expressed genes (DEGs) in diabetic and nondiabetic microvessels were identified by cDNA microarrays analysis. In RMVs, we identified 43 DEGs, of which 20 were upregulated while 23 were downregulated by diabetes. In BMVs, 35 genes DEGs were identified, of which 22 were upregulated and 13 were downregulated by diabetes. Altered expression of the Nars, Gars, Mars, Iars, Yars, Bcl2, Nqo1, NR4A3, Gpd1, Stc1, Tsc22d3, Tnfrsf21 mRNA as observed in the microarray analyses, was confirmed by quantitative RT-PCR. The aminoacyl-tRNA synthetases (aaRSs) pathway in RMVs was significantly overrepresented as compared to BMVs. Our study demonstrates for the first time that in the brain microvasculature multiple compensatory mechanisms exists, serving to protect brain tissue from diabetic insults, whereas these mechanisms are not activated in the retinal microvasculature. This provides new insights as to why brain microvasculature is less susceptible to diabetes.

SUBMITTER: Li Y

PROVIDER: S-EPMC9982389 | biostudies-literature | 2023 Jan-Feb

REPOSITORIES: biostudies-literature

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Responses of retinal and brain microvasculature to streptozotocin induced diabetes revealed by global expression profiling.

Li Youhai Y Faiz Alen A Moshage Han H Schilling Lothar L Kamps Jan Aam JA

Diabetes & vascular disease research 20230101 1

This study aims to determine the effects of diabetes in the retinal and brain microvasculature through gene expression profiling. Twelve male Wistar rats were randomly divided into two groups: streptozotocin-induced diabetic rats and time-matched nondiabetic rats. The retinal microvessels (RMVs) and brain microvessels (BMVs) were mechanically isolated from individual rats. Differentially expressed genes (DEGs) in diabetic and nondiabetic microvessels were identified by cDNA microarrays analysis. ...[more]

PMID: 36606460

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Project description:PurposeTo reveal the causality between retinal vascular density (VD), fractal dimension (FD), and brain cortex structure using Mendelian randomization (MR).DesignCross-sectional study.ParticipantsGenome-wide association studies of VD and FD involving 54 813 participants from the United Kingdom Biobank were used. The brain cortical features, including the cortical thickness (TH) and surface area (SA), were extracted from 51 665 patients across 60 cohorts. Surface area and TH were measured globally and in 34 functional regions using magnetic resonance imaging.MethodsBidirectional univariable MR (UVMR) was used to detect the causality between FD, VD, and brain cortex structure. Multivariable MR (MVMR) was used to adjust for confounding factors, including body mass index and blood pressure.Main outcome measuresThe global and regional measurements of brain cortical SA and TH.ResultsAt the global level, higher VD is related to decreased TH (β = -0.0140 mm, 95% confidence interval: -0.0269 mm to -0.0011 mm, P = 0.0339). At the functional level, retinal FD is related to the TH of banks of the superior temporal sulcus and transverse temporal region without global weighted, as well as the SA of the posterior cingulate after adjustment. Vascular density is correlated with the SA of subregions of the frontal lobe and temporal lobe, in addition to the TH of the inferior temporal, entorhinal, and pars opercularis regions in both UVMR and MVMR. Bidirectional MR studies showed a causation between the SA of the parahippocampal and cauda middle frontal gyrus and retinal VD. No pleiotropy was detected.ConclusionsFractal dimension and VD causally influence the cortical structure and vice versa, indicating that the retinal microvasculature may serve as a biomarker for cortex structural changes. Our study provides insights into utilizing noninvasive fundus images to predict cortical structural deteriorations and neuropsychiatric disorders.Financial disclosuresThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Responses of retinal and brain microvasculature to streptozotocin induced diabetes revealed by global expression profiling.

Publications

Responses of retinal and brain microvasculature to streptozotocin induced diabetes revealed by global expression profiling.

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