Intraocular Properties of a Repository Urokinase Receptor Antagonist Å36 Peptide in Rabbits

Purpose: To evaluate the intraocular properties of A36, a peptide that directly antagonizes the cell surface urokinase receptor and so prevents pericellular urokinase plasminogen activator activity.Methods: A total of 41 rabbits were used. The toxicity study tested three doses of A36: 1 mg/ eye, 0.3 mg/eye, and 0.1 mg/eye. At 2 and 12 weeks, eyes were evaluated by ERG and histology. Pharmacokinetics were studied in rabbit eyes with the dose of 1 mg/eye in two different formulations: a micronized preparation and a non-micronized formulation. Eyes were enucleated at months 1, 2, 3, 4, and 5. Vitreous, retina, and choroid were collected separately for active A36 analysis.Results: We did not find ocular toxicity with low and medium doses. At the highest dose, there was a transient toxicity at 2 weeks but was not notable at 3 months. The target choroid concentration of A36 was chosen as ≥100 nM. The micronized formulation at months 1, 2, and 3 combined, showed variable levels in the choroid giving 5/10 (50%) o...