The mechanisms underlying IOP-mediated degeneration of retinal ganglion cells (RGCs) is unclear.

This study investigated whether plasminogen activators play a role in RGC degeneration in a mouse model of POAG.

IOP elevation led to an up-regulation in tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and their receptor LRP-1, and promoted significant degeneration of RGCs.

Inhibition of tPA and uPA binding to LRP-1 or inhibition of their proteolytic activity attenuated IOP-mediated degeneration of RGCs.

These results suggest that tPA and uPA play a significant role in IOP-mediated degeneration of RGCs.