Distribution of TNP-470 in Rabbit Aqueous Humor and Its Effect on Neovascularization after High-risk Corneal Transplantation

Objective To investigate the concentrations of O-(chloracetyl-carbamoyl)fumagillol(TNP-470)in rabbit aqueous humor after local administration,and to observe the effect of TNP-470 on neovascularization after high-risk penetrating keratoplasty(PK).Methods Corneal neovascularization was induced in 30 New Zealand white rabbits by NaOH.Donor corneas from 10 rabbits were transplanted into 20 recipients of corneal grafts.The animal model of high-risk corneal transplantation was successfully established in 16 rabbits.These rabbits were randomly divided into four groups,with 4 rabbits in each group.Group A was not given drug treatment.Group B,C and D were topically administered with TNP-470 at concentrations of 100,500 and 1 000ng.mL-1(1drop per time,6times per day)for 90 days,respectively.Drug concentrations in aqueous humor were measured by high performance liquid chromatography(HPLC)at 1,2,7,14,28 and 56 days after the start of drug treatment.Corneal allografts were examined every other day and neovascularization index(NI) were recorded at 2,6,9 and 12 weeks after transplantation.Results TNP-470 was found in aqueous humor at each time point,and there were significant differences in TNP-470 concentrations among the three experimental groups(P0.05).In group A,NI increased at 2 weeks after transplantation and was maintained at a higher level after 6 weeks.However,NI was maintained at a lower level at 6 weeks after transplantation in group B,C and D.The differences were significant between experimental groups and group A(P0.05).Conclusion Ophthalmic administration of TNP-470 can inhibit corneal neovascularization after high-risk corneal transplantation in rabbits.