Fibrin: mediator of in vivo and in vitro injury and inflammation.

We examined the role that fibrin deposition and fibrin-associated factors (FAF) play in acute anterior segment inflammatory responses in the rabbit eye. It was demonstrated by immunofluorescence that fibrin represented a major component of the exudative meshwork deposited within the anterior chamber and on leukocyte surfaces therein. Using our in vivo model of endocular inflammation we next demonstrated that fibrin and fibrinogen-derived peptides, but not thrombin, induced inflammatory responses characterized by both leukocyte influx and endothelial cell injury. Fibrin formation within the anterior chamber induced a leukocyte influx consisting primarily of PMN's. Fibrinogen-derived peptides induced primarily a monocyte influx. This dichotomy suggests that multiple inflammatory mediators are elaborated or released during endocular fibrinogenesis and fibrinolysis. To investigate direct effects of fibrin deposition on the corneal endothelial cells (CEC) an in vitro "corneal cup" organ culture model was next developed. Studies comparing various types of mediators demonstrated that only fibrin- derived preparations directly induced CEC injury. Fibrin deposition may thus play multiple roles in endocular inflammation, including the modulation of leukocyte influx, and the direct mediation of corneal endothelial cell injury.