Expression of TGF-ß1 and TGF-ß2 in Failed Filtering Blebs of Patients with Pseudoexfoliation and Primary Open-angle Glaucoma

Abstract

Abstract: : Purpose: Transforming growth factor (TGF)-ß1 and TGF-ß2 are potent stimulators of proliferation, migration and matrix production of human Tenon's capsule fibroblasts in vitro suggesting a significant influence on the conjunctival scarring response after glaucoma filtration surgery. In addition to significantly increased aqueous humor levels of TGF-ß1 in pseudoexfoliation (PEX)-syndrome/glaucoma and TGF-ß2 in primary open-angle glaucoma (POAG), local production of both isoforms by resident cells at the filtering site may adversely affect the outcome of glaucoma filtration surgery. We therefore investigated the expression of TGF-ß1 and TGF-ß2 together with their binding protein LTBP-1 in failed filtering blebs in comparison with normal conjunctival specimens. Methods: Five failed filtering blebs obtained from patients with PEX glaucoma and POAG, who had undergone revision surgery, and normal conjunctival biopsies with Tenon's capsule were processed for light microscopic immunohistochemistry using antibodies against TGF-ß1, TGF-ß2 and LTBP-1. Results: In normal conjunctival specimens, only TGF-ß2 was present in the conjunctival and subconjunctival stromal fibroblasts, whereas TGF-ß1 was confined to the basal cells of the conjunctival epithelium. In both POAG and PEX glaucoma, TGF-ß1 levels were increased in the subepithelial extracellular matrix of the filtering blebs and colocalized with LTBP-1 in the stroma. TGF-ß2 immunoreactivity was also increased but still localized to epithelial cells and stromal fibroblasts and not to the extracellular matrix. Conclusions: These findings suggest that scarred filtering blebs are associated with a significant stromal level of TGF-ß1 suggesting that TGF-ß1 in addition to TGF-ß2 may have a key role in the pathogenesis of the conjunctival wound healing response after glaucoma filtration surgery of patients with PEX glaucoma and POAG. Colocalization of TGF-ß1 with LTBP-1 indicates binding of TGF-ß1 to the extracellular matrix, which may serve as a repository of TGF-ß1. Anti-TGF-ß1 therapy may, therefore, be another useful strategy for reducing postoperative conjunctival scarring.

Keywords: wound healing • conjunctiva • growth factors/growth factor receptors