INTRAVITREAL TRANSFORMING GROWTH-FACTOR-BETA-2 DECREASES CELLULAR INFILTRATION IN ENDOTOXIN-INDUCED OCULAR INFLAMMATION IN RABBITS

Transforming growth factor-beta (TGF-beta), a multifunctional cytokine which has been identified in normal and inflamed ocular fluids, may p lay a role in the evolution of inflammatory ocular lesions. In this st udy we utilized a rabbit model of LPS-induced uveitis to determine if exogenous TGF-beta 2 could alter its course. Recombinant TGF-beta 2 (1 -2000 ng), LPS (10 or 20 ng), or TGF-beta 2 (100 ng) plus LPS (10 ng) were injected intravitreally in one eye of a New Zealand white rabbit and the contralateral eye served as a paired control which received an equal volume of vehicle. The uveitic response was assessed by biomicr oscopic examination of the anterior uvea and analysis of protein and c ells in the aqueous humor. Ocular tissues were processed for histologi c, immunohistochemical and in situ hybridization analyses. Rabbits inj ected with doses of TGF-beta 2 greater than or equal to 500 ng develop ed a mild uveitic response, compared to LPS alone, accompanied by expr ession of IL-1 beta mRNA and protein in the anterior uvea. Interesting ly, rabbits coinjected with LPS (10 ng) and a nonuveitic dose (100 ng) of TGF-beta 2 exhibited a similar increase in ocular vascular permeab ility, but a decrease in inflammatory cell infiltration into the anter ior uvea and aqueous humor (1185 +/- 117 versus 2465 +/- 176; p < 0.05 ). No evidence of inflammation was observed in eyes injected with 100 ng TGF-beta 2 alone. Similar to other models of inflammation, TGF-beta may interrupt the cascade of events leading to ocular inflammation, t hereby suggesting therapeutic potential.