EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA IN EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION

Purpose. Transforming growth factor beta (TGF-beta) is a multifunction al cytokine that modulates biological events as diverse as wound heali ng and angiogenesis and which may be important in the pathogenesis of choroidal neovascularization. We investigated the mRNA expression of T GF-beta isoforms in a model of experimental choroidal neovascularizati on induced by krypton-laser photocoagulation. Methods. Rat TGF-beta 1, mouse TGF-beta 2 or TGF-beta 3 cDNAs was inserted into the pBluescrip t vector to prepare antisense and sense riboprobes. Intense laser burn s were applied to the posterior poles of the eyes of pigmented rats ac cording to a protocol described for producing choroidal neovasculariza tion in these animals. At intervals up to 4 weeks after photocoagulati on, the eyes were obtained and cut into thin sections. The sections we re subjected to in situ hybridization with digoxigenin (DIG)-labeled s ingle-strand riboprobes synthesized from each TGF-beta cDNA. Results. In normal adult rat retinas and choroids, TGF-beta 1 mRNA was found on ly in cells of the ganglion cell layer, TGF-beta 2 mRNA was found in c ells of the ganglion cell layer and choriocapillaris endothelium, wher eas TGF-beta 3 mRNA was not detected at all. During the process of neo vascularization, TGF-beta 1 and TGF-beta 2 mRNAs (the latter being exp ressed more prominently) were detected in retinal pigment epithelial s ells, fibroblast-like cells and the endothelium of the neovascular reg ion. TGF-beta 2 was the predominant isoform of TGF-beta, and its expre ssion was especially strong in the endothelium of the choroidal neovas cularization at 2 weeks. However, TGF-beta mRNAs was decreased in cell s 4 weeks after photocoagulation. Conclusions. Our findings suggest th at TGF-beta may act in the retina as a neurotrophic agent, since TGF-b eta 1 is normally transcribed in ganglion cells and TGF-beta 2 is also transcribed in ganglion cells and choriocapillaris endothelium. TGF-b eta 1 and TGF-beta 2 mRNA expression were increased in photocoagulated lesions from 3 days to 2 weeks after laser treatment. Therefore, it i s likely that TGF-beta acts as a mediator of the neovascularization pr ocess.