BACKGROUND: In many species intraocular inflammation is accompanied by fibrin clot formation, which can lead to the formation of synechia, secondary glaucoma and visual impairment. Tissue-plasminogen activator (t-PA) is routinely injected into the eye to dissolve fibrin. This drug showed varying corneoscleral permeability in different species and did not reach clinically efficacious intraocular concentrations in dogs after topical application. Another similar fibrinolytic agent, identified in vampire bat saliva, is a smaller but structurally similar molecule with a higher fibrin selectivity, longer half-life and better biocompatibility compared to t-PA. It reached clinical trials in human stroke patients but has not been tested for its ophthalmological use.
SPECIFIC AIMS: To perform a prospective ex vivo study to evaluate the corneal and scleral permeability for the substitute of t-PA in rabbit, canine, equine, porcine and human tissue.
SIGNIFICANCE: The study will evaluate if and via which route the potential t-PA substitute permeates ocular tissue of different species. In addition to providing pharmacological information, the data can be used to design future drug permeability and efficacy studies. Topical application of a fibrinolytic drug with a similar or higher fibrinolytic capacity, a longer half-life and a better biocompatibility than intracamerally applied t-PA could potentially change the therapeutic standard for fibrinous uveitis in veterinary and human ophthalmology.