Target gene transfer of tissue plasminogen activator to cornea by electricpulse inhibits intracameral fibrin formation and corneal cloudiness

Intracameral fibrin formation, a complication of ocular inflammation and in traocular operations, sometimes results in glaucoma and/or corneal damage l eading to permanent visual loss. We transferred a therapeutic gene to the c orneal endothelium in order to use it as a therapeutic organ. A plasmid enc oding tissue plasminogen activator (tPA) was injected into the anterior cha mber of rats and electric pulses (EPs) were given subsequently, which trans ferred a plasmid gene to a highly selected area of corneal endothelium with no inflammation. The biologically active tPA was clearly present for 4 day s after treatment. Fibrin formation induced by YAG laser-generated bleeding in the anterior chamber decreased significantly more in treated eyes than in control eyes. Corneal opacity was significantly lower in treated eyes th an in control eyes and histological damage was not apparent in the treated eyes. This genetic modification allows us to use the corneal endothelium to treat various ocular diseases and could be a new and effective type of pha rmacologic gene therapy.