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E Sakurai, M Nozaki, N Kunou, T Okabe, H Kimura, Y Ogura; Scleral Plug of Biodegradable Polymers Containing Immunosuppressant for Experimental Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2296.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the efficacy of a biodegradable scleral plug containing FK-506 in a rabbit model of experimental uveitis. Methods: We prepared the scleral plugs by dissolving poly (DL-lactide-co-glycolide) (PLGA) and FK-506 (weight 8.5mg, length 5mm, 1% FK506). The release of FK-506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK-506 concentrations of the aqueous humors and vitreous were measured by high performance liquid chromatography following plug implantation in pigmented rabbits (2, 4, 8, and 12 weeks after intravitreous implantation). Twenty pigmented rabbits were immunized twice subcutaneously with 10mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, scleral plugs were implanted into the vitreous of the right eye of 10 rabbits. Ten control rabbits received a sham device. One day after later, the right eye of all rabbits were challenged with an intravitreal injection of 50 µg of antigen. The aqueous protein concentrations and cell counts were determined on post-challenge days 7 and 13. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 15 and were observed for 3 months. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Results: The in vitro release studies showed stable, long term sustained and slow release (released % were 0.78, 1.56, 2.38, 3.06, 20.4, and 39.9 %, respectively). The in vivo release studies showed that the scleral plug had long-term release for vitreous and aqueous humors. Scleral plug was effective in delivering significantly higher drug concentration to each ocular tissues (470-290 ng /g) at all time points. Clinical scores of treated eyes had significantly less inflammation than untreated eyes (P<0.01). Quantitative analysis of inflammatory cells (P<0.01) and protein concentrations (P<0.01) in the anterior chamber showed a significant decrease in treated eyes. After antigen rechallenged, inflammation in experimental eyes was still less than in control eyes. Conclusion: The intravitreal-sustained release of biodegradable polymers containing FK506 device is highly effective in suppressing inflammation experimental uveitis in a rabbit model. This device may be useful in the management of patients with severe chronic uveitis.
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