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To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b ϩ /LYVE-1 ϩ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II hi ) antigen-presenting cells to the lymphoid compartment.Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (PϽ.001) and lymphatic caliber (PϽ.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b ϩ /LYVE-1 ϩ monocytic cells to the cornea and homing of mature CD11b ϩ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion:Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

Cortical networks generate temporally correlated brain activity. To clarify the functional significance of this correlated activity, we asked whether and how its structure depends on stimulus and arousal state. Using independent components analysis of macaque functional magnetic resonance imaging data, we identified a large number of brain networks that were strikingly reproducible across different visual stimulus contexts. Fewer networks were reproducible across alert and anesthetized brain states. Network complexity ranged from bilateral single-node networks to networks comprising multiple discrete nodes distributed over 3 cm of cortex; one network identified in our survey included parts of the temporal parietal occipital junction, dorsal premotor cortex, insula, and posterior cingulate cortex bilaterally. Our results reveal the wealth of spatially structured correlated networks throughout the brain in both alert and anesthetized monkeys, and show that anesthesia significantly alters the spatial structure of these networks.

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