FYN regulates aqueous humor outflow and IOP through the phosphorylation of VE-cadherin.

The exact sites and molecules that determine resistance to aqueous humor drainage and control intraocular pressure (IOP) need further elaboration. Proposed sites include the inner wall of Schlemms's canal and the juxtacanalicular trabecular meshwork ocular drainage tissues. The adherens junctions (AJs) of Schlemm's canal endothelial cells (SECs) must both preserve the blood-aqueous humor (AQH) barrier and be conducive to AQH drainage. How homeostatic control of AJ permeability in SC occurs and how such control impacts IOP is unclear. We hypothesized that mechano-responsive phosphorylation of the junctional molecule VE-CADHERIN (VEC) by SRC family kinases (SFKs) regulates the permeability of SEC AJs. We tested this by clamping IOP at either 16 mmHg, 25 mmHg, or 45 mmHg in mice and then measuring AJ permeability and VEC phosphorylation. We found that with increasing IOP: 1) SEC AJ permeability increased, 2) VEC phosphorylation was increased at tyrosine-658, and 3) SFKs were activated at the AJ. Among the two SFKs known to phosphorylate VEC, FYN, but not SRC, localizes to the SC. Furthermore, FYN mutant mice had decreased phosphorylation of VEC at SEC AJs, dysregulated IOP, and reduced AQH outflow. Together, our data demonstrate that increased IOP activates FYN in the inner wall of SC, leading to increased phosphorylation of AJ VEC and, thus, decreased resistance to AQH outflow. These findings support a crucial role of mechanotransduction signaling in IOP homeostasis within SC in response to IOP. These data strongly suggest that the inner wall of SC partially contributes to outflow resistance.

Social factors influence solo and rat dyads exploration of an unfamiliar open field.

Exploring new and unfamiliar environments is critical for survival, providing information on food, shelter, mates, and sources of danger. The open field paradigm is commonly used to study exploration and anxiety-like behaviors in the lab. Many social animals, like humans and rats, may explore their environments in social groups; however, relatively few studies have investigated the influence of conspecifics on open field activity. Here, we provide a comparison of individual (solo) or pairs of male rats (dyads) exploring and interacting across repeated exposures to an unfamiliar (Day 1) or more familiar (Day 2) open field. Both solo rats and dyads explored a larger area, traveled further, and spent less time near the maze walls on the second maze exposure. Solo rats explored a larger area and spent less time near the maze walls than dyads on both days because dyads spent more time socializing rather than exploring the environment. Furthermore, we compared familiar dyads that were co-housed for seven days versus stranger dyads that met for the first time in the open field. While familiar and stranger dyads did not differ in maze exploration, strangers spent more time interacting nose to nose than nose to anogenital. These results indicate that the degree of familiarity with the environment does not interact with the tendency of dyads to socialize rather than explore the environment.