Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat

Curr Eye Res. 1995 Mar;14(3):209-14. doi: 10.3109/02713689509033516.

Abstract

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

MeSH terms

  • Administration, Topical
  • Animals
  • Anterior Eye Segment / drug effects
  • Anterior Eye Segment / pathology
  • Aqueous Humor / chemistry
  • Cell Adhesion Molecules / analysis
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endotoxins
  • Eye Proteins / analysis
  • Female
  • Immunoenzyme Techniques
  • Ophthalmic Solutions
  • Rats
  • Rats, Inbred Lew
  • Salmonella typhimurium
  • Tacrolimus / administration & dosage
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use*
  • Uveitis, Anterior / chemically induced
  • Uveitis, Anterior / pathology
  • Uveitis, Anterior / prevention & control*

Substances

  • Cell Adhesion Molecules
  • Endotoxins
  • Eye Proteins
  • Ophthalmic Solutions
  • Tacrolimus