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Effects of TGF-ß1 and TGF-ß2 on Proliferation, Migration and Matrix Production of Cultured Human Tenon's Capsule Fibroblasts in Pseudoexfoliation and Primary Open Angle Glaucoma
1Kottler U. B., 2Schlötzer-Schrehardt U., 2Zenkel M., 2Küchle M., 2Jünemann A., 2Naumann G. O. H.,
1Johannes-Gutenberg-Universität Mainz, Universitäts-Augenklinik (Erlangen)
2Friedrich-Alexander-Universität, Augenklinik (Erlangen)
Purpose: Significantly increased aqueous levels of TGF-ß1 in pseudoexfoliation (PEX) syndrome/glaucoma and TGF-ß2 in primary open-angle glaucoma (POAG) may adversely affect the outcome of glaucoma filtration surgery. We investigated the effects of TGF-ß1 and -ß2 on proliferation, migration and extracellular matrix production of cultured Tenon's capsule fibroblasts derived from PEX, POAG, and cataract control patients.
Methods: Tenon's capsule fibroblasts were cultured and stimulated with TGF-ß1 or -ß2 at concentrations from 0.01 to 20 ng/ml for 1 to 14 days. Cell proliferation was determined with the WST-1 colorimetric assay; extracellular matrix (fibronectin, collagen types I and III) production was assessed by immunoassays and cell migration by migration assays.
Results: TGF-ß1 and TGF-ß2 stimulated cell proliferation and extracellular matrix production of Tenon's capsule fibroblasts in a characteristic dose-dependent manner; the two isoforms had no significantly different effects on proliferation. Fibronectin synthesis was increased about 5 times, and the level of collagen I was elevated by factor 10. Whereas both isoforms had a similar effect on matrix production in POAG, TGF-ß1 predominated in PEX syndrome/glaucoma. TGF-ß2 stimulated cell migration in both glaucoma groups.
Conclusions: These findings indicate that TGF-ß1 and -2 in pathophysiologic concentrations are potent stimulators of proliferation and matrix production of human Tenon's capsule fibroblasts, suggesting that both isoforms may significantly influence the conjunctival scarring response after glaucoma filtration surgery. Because TGF-ß1 was more effective in stimulating matrix synthesis in PEX fibroblasts, anti-TGF-ß1 therapy may be a useful strategy for reducing conjunctival scarring in eyes with PEX glaucoma.