Glucocorticoids are a vital class of endogenous steroid hormones that regulate essential biological processes including growth, development, metabolism, behavior and apoptosis. Most, if not all, of these actions are thought to be mediated through the glucocorticoid receptor. The exact mechanisms of how one hormone, via one receptor, modulates such diverse biological functions are largely unknown. However, recent studies from our lab and others have suggested that a contribution for the diversity results from multiple isoforms of the glucocorticoid receptor that result from alternative RNA splicing and translation initiation of the glucocorticoid receptor mRNA. Additionally, each isoform is subject to several post-translational modifications, including phosphorylation, ubiquitination and sumoylation, which have been shown to modulate the receptor protein stability and/or function. Together these data provide potentially diverse mechanisms to establish cell type specific regulation of gene expression by a single transcription factor. Here, we summarize the recent advances and processes that generate these receptor isoforms and these post-translational modifications. We speculate that the composition and proportion of individual isoforms expressed in particular cellular contexts account for the diverse effects of glucocorticoid hormones.
Purpose
This study was conducted to determine blood flow velocities and corresponding vessel diameters to characterize the response of the bulbar conjunctival microvasculature to contact lens wear.
Methods
A Functional Slit-lamp Biomicroscope (FSLB), an adapted traditional slit-lamp, was used to image the temporal bulbar conjunctiva of 22 healthy subjects before and after 6 hours of contact lens wear. All of the measurable venules on the conjunctiva were processed to yield vessel diameters and blood flow velocities.
Results
The averaged blood flow velocity increased from 0.51 ± 0.20 mm/s to 0.65 ± 0.22 mm/s (P < 0.001) after 6 hours of lens wear. The blood flow velocity distribution showed a velocity increase that correlated with the vessel diameter increase from the baseline (r = 0.826, P < 0.05). This pattern maintained a similar trend after 6 hours of lens wear (r = 0.925, P < 0.05), and increased velocities were found across all of the vessel diameter ranges (P < 0.001).
Conclusions
Blood flow velocity increases across all of the vessel diameter ranges in response to contact lens wear. FSLB is capable of characterizing the bulbar microvascular response to contact lens wear.
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