Management of Glaucoma in Pregnancy.

Management of glaucoma during pregnancy represents a challenge for the physician. Important disease and patients' health decisions begin even before conception and continue throughout pregnancy and breastfeeding. The data on this topic is limited due to ethical and legal constraints and challenges of conducting large, prospective, and randomized clinical trials on this patient population. Our review suggests that individually, intraocular pressure is lower in a pregnant woman when compared with a nonpregnant woman. Importantly, the medical management of glaucoma during pregnancy poses special challenges due to the possibility of adverse effects of medications on the fetus and newborn. Laser trabeculoplasty and traditional filtration surgery, and minimally invasive glaucoma surgery, represent nondrug management options. Thus, managing glaucoma in pregnancy is a delicate balance between treatment to prevent damage to the optic nerve in the mother and avoidance of interventions potentially harmful to the fetus. This literature review of published individual and population-based studies was performed to explore current knowledge and guidelines in the management of glaucoma in pregnancy.

AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol.

AMP-activated protein kinase (AMPK) enhances glucose transporter GLUT4 regulation. AMPK also suppresses energy-consuming pathways such as cholesterol synthesis. Interestingly, recent in vitro and in vivo data suggest that excess membrane cholesterol impairs GLUT4 regulation. Therefore, this study tested whether a beneficial, GLUT4-regulatory aspect of AMPK stimulation involved cholesterol lowering. Using L6 myotubes stably expressing an exofacial myc-epitope-tagged-GLUT4, AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-ß-d-ribonucleoside (AICAR; 45 min, 1 mm) or 2,4-dinitrophenol (DNP; 30 min, 200 µm) increased cell surface GLUT4myc labeling by approximately ≈ 25% (P < 0.05). Insulin (20 min, 100 nm) also increased GLUT4myc labeling by about 50% (P < 0.05), which was further enhanced (≈ 25%, P < 0.05) by AICAR or DNP. Consistent with AMPK-mediated suppression of cholesterol synthesis, AICAR and DNP decreased membrane cholesterol by 20-25% (P < 0.05). Whereas AMPK knockdown prevented the enhanced basal and insulin-stimulated GLUT4myc labeling by AICAR and DNP, cholesterol replenishment only blocked the AMPK-associated enhancement in insulin action. Cells cultured in a hyperinsulinemic milieu, resembling conditions in vivo that promote the progression/worsening of insulin resistance, displayed an increase in membrane cholesterol. This occurred concomitantly with a loss of cortical filamentous actin (F-actin) and defects in GLUT4 regulation by insulin. These derangements were prevented by AMPK stimulation. Examination of skeletal muscle from insulin-resistant Zucker rats revealed a similar elevation in membrane cholesterol and loss of F-actin. Lowering cholesterol to control levels restored F-actin structure and insulin sensitivity. In conclusion, these data suggest a novel aspect of GLUT4 regulation by AMPK involves membrane cholesterol lowering. Moreover, this AMPK-mediated process protected against hyperinsulinemia-induced insulin resistance.