Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis.
OBJECTIVE
To evaluate the efficacy of a biodegradable polymeric scleral plug containing the immunosuppressive agent, FK506, in a rabbit model for experimental uveitis.


METHODS
The scleral plugs were prepared by dissolving poly(DL-lactide-co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high performance liquid chromatography 2 and 4 weeks after intravitreous plug implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, the right eyes of all rabbits were challenged with an intravitreal injection of 50 micro g of antigen. After the first challenge, the 16 eyes of 16 pigmented rabbits were divided into two groups. Scleral plugs were implanted into the vitreous of the right eye of eight rabbits. Eight control rabbits received a sham device. The aqueous protein concentrations and cell counts were determined on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 14 and were observed for 1 month. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG) and histologic examination.


RESULTS
Clinical scores (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes had significantly less inflammation than untreated eyes (P<0.001). Quantitative analysis of inflammatory cells (P<0.001) and protein concentrations (P<0.0001) in the anterior chamber showed significant decreases in treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated eyes. No retinal toxicity was detected, histopathologically and electroretinographically. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes.


CONCLUSIONS
Intravitreal sustained-release of FK506 from a biodegradable polymeric scleral plug was highly effective in suppressing the inflammation of experimental uveitis in a rabbit model for at least 6 weeks. This device may be useful in the management of patients with severe chronic uveitis.
Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan.
Eiji
E
Sakurai
Miho
M
Nozaki
Komei
K
Okabe
Noriyuki
N
Kunou
Hideya
H
Kimura
Yuichiro
Y
Ogura
D020341:Absorbable Implants; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D001672:Biocompatible Materials; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004596:Electroretinography; D005136:Eye Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D012590:Sclera; D012599:Sclerostomy; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology
D000942:Antigens, Bacterial; D001672:Biocompatible Materials; D005136:Eye Proteins; D007166:Immunosuppressive Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016559:Tacrolimus