THE ROLE OF FREE-RADICALS IN PARAQUAT-INDUCED CORNEAL LESIONS

Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redox-cycling of paraquat generates oxyge n radicals. The toxic, even lethal, effects of paraquat are due to fre e radical-mediated tissue injury. Ocular lesions, sometimes quite seve re, have been observed following accidental splashing of paraquat solu tions onto the eyes. These studies were designed to document the gener ation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals ( rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. afte r intrastromal injection of paraquat, showed the signal of the free ra dical of paraquat. Ultrastructural studies of corneas 8 days after int rastromal injections (100 mu l) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. I n rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement mem brane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits t o the effects of paraquat. No lesions were observed following intrastr omal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the prox imal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significa nt plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabb it and monkeys as well as possible biochemical differences may account for the species differences observed.