Fig. 1. Purinergic regulation of aqueous humor outflow.
The present aim was to identify which of the mechanisms thought to subserve ATP release in other preparations might underlie release by TM cells. The current results indicate that PX1, Cxs and P2RX7 play major roles, but not CFTR, VSOR, the maxi-anion channel or vesicular release. Following release, ATP can directly activate multiple P2X and P2Y receptors to initiate downstream purinergic signaling, or can be ecto-enzymatically degraded into adenosine, stimulating A1AR-mediate matrix metalloproteinase 2 (MMP-2) secretion. The MMP-2 lowers outflow resistance, thereby reducing intraocular pressure.