Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.
These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.
Purpose. The study hypothesis was that shear stress caused by abnormal aqueous flow is one of the causes of corneal endothelial cell loss after laser iridotomy (LI). The shear stress exerted on the corneal endothelial cells (CECs) in anterior chambers (ACs) of different depths was calculated by a computational fluid dynamics program. The effect of shear stress was also examined on human corneal endothelial cells (HCECs) grown on microscope slides. Methods. Three-dimensional models of the AC were constructed, with and without an LI window, and AC depths of 2.8, 1.8, 1.5, and 1.0 mm. The speed of aqueous streaming through the LI window was obtained from animal studies and used to calculate the shear stress exerted on the CECs. Cultured HCECs attached to glass slides were subjected to different magnitudes of shear stress by exposing the cells to different flow rates of the culture solution. The number of cells remaining attached to the slide under each condition was determined. Results. The shear stresses were 0.14, 0.31, 0.48, and 0.70 dyn/cm(2) for models with AC depths of 2.8, 1.8, 1.5, and 1.0 mm, respectively. When cultured HCECs were subjected to shear stress within the range calculated by the three-dimensional models, the number of cells remaining attached to the glass slide decreased as the magnitude and duration of the shear stress increased. Conclusions. Shear stress exerted on CECs after LI may reach a magnitude high enough to cause cell damage and loss in eyes, especially in those with shallow anterior chambers.
Background: In Japan, intravitreal anti-vascular endothelial growth factor (anti-VEGF) dosing regimens for wet age-related macular degeneration (wAMD) include pro re nata, every 2 months, and treat-and-extend, resulting in different outcomes and patient burden. Although reflecting patient preferences in treatment decision-making is desirable, few studies have examined this in Japan. This study assessed the patients willingness to trade-off between different dosing regimens. Patients and Methods: Patients with wAMD were recruited from four Japanese university hospitals to complete a face-to-face cross-sectional survey. In a discrete choice experiment, patients were asked to choose their preferred option from two anti-VEGF treatment profiles shown side-by-side across a series of choice tasks. The profiles varied on four attributes: number of injections in 12 months, number of physician consultations in 12 months, chance of 1-year visual acuity (VA) improvement, and chance of 2-year VA maintenance. Preference weights were estimated using hierarchical Bayes' models. Results: Overall, 120 patients (30 treatment naïve and 90 anti-VEGF experienced) completed the survey. Patients were willing to accept an increase from three to approximately eight injections in 12 months to increase the chance of 1-year VA improvement from 25% to 40%. They would be willing to accept 11 injections in 12 months if the chance of 2-year VA maintenance increased from 80% to 96%. The most valued attributes were increasing the chance of 2-year VA maintenance and reducing the number of injections in 12 months, which were each about twice as important as decreasing physician consultations in 12 months and increasing the chance of 1-year VA improvement (p<0.001). Among the dosing regimens, patients most preferred treat-and-extend because of its higher chance of 2-year VA maintenance. Conclusion: Informing patients with wAMD about the likelihood of long-term VA maintenance when selecting treatment may increase the acceptance of an optimal treatment regimen and number of injections.
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