Abstract
Although retinal microvessels (RMVs) and brain microvessels (BMVs) are closely related in their developmental and share similar blood-neural barriers, studies have reported markedly different responses to stressors such as diabetes. Therefore, we hypothesized that RMVs and BMVs will display substantial differences in gene expression levels even though they are of the same embryological origin. In this study, both RMVs and BMVs were mechanically isolated from rats. Full retinal and brain tissue samples (RT, BT) were collected for comparisons. Total RNA extracted from these four groups were processed on Affymetrix rat 2.0 microarray Chips. The transcriptional profiles of these tissues were then analyzed. In the present paper we looked at differentially expressed genes (DEGs) in RMVs (against RT) and BMVs (against BT) using a rather conservative threshold value of ≥ ± twofold change and a false discovery rate corrected for multiple comparisons (p < 0.05). In RMVs a total of 1559 DEGs were found, of which 1004 genes were higher expressed in RMVs than in RT. Moreover, 4244 DEGs between BMVs and BT were identified, of which 1956 genes were ≥ twofold enriched in BMVs. Using these DEGs, we comprehensively analyzed the actual expression levels and highlighted their involvement in critical functional structures in RMVs and BMVs, such as junctional complex, transporters and signaling pathways. Our work provides for the first time the transcriptional profiles of rat RMVs and BMVs. These results may help to understand why retina and brain microvasculature show different susceptibilities to stressors, and they might even provide new insight for pharmacological interventions.
Highlights
Retinal microvessels (RMVs) and brain microvessels (BMVs) are closely related in their developmental and share similar blood-neural barriers, studies have reported markedly different responses to stressors such as diabetes
In the present paper we looked at differentially expressed genes (DEGs) in retinal microvessels (RMVs) and BMVs using a rather conservative threshold value of ≥ ± twofold change and a false discovery rate corrected for multiple comparisons (p < 0.05)
The gene expression data were at first analyzed by principal components analysis (PCA) which revealed 4 clusters with wide separation of retina tissue (RT) and brain tissue (BT) samples and somewhat less but still clear distinction of the RMVs and BMVs samples (Fig. 1)
Summary
Retinal microvessels (RMVs) and brain microvessels (BMVs) are closely related in their developmental and share similar blood-neural barriers, studies have reported markedly different responses to stressors such as diabetes. We have previously developed a method, which allows high yield high purity isolation of the microvascular compartment from rat brain and retina We characterized these isolates histologically and by semi-quantitative real time polymerase chain reaction (qRT-PCR) methodology which showed significant enrichment of markers of microvascular-specific cells and a distinct depletion of parenchymal cell markers (covering neuronal, astrocytic, and photoreceptor cells) compared to full tissues[13]. Based on these results we have performed a transcriptome-wide analysis to systematically compare RMVs and BMVs obtained from the same group of rats We hypothesize that these two types of MVs will display substantial differences in gene expression levels even though they are of the same embryological origin. This heterogeneity at the transcriptome level may translate into differences in physiological responses, and it may play a role in the differential susceptibility of the iBRB and BBB to stressors like high blood glucose
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