Long-Term Topical Antiglaucoma Medications Cause Enhanced Tenon's Capsule Fibroblast Proliferation and Abnormal TGF-β and MMP Expressions: Potential Effects on Glaucoma Filtering Surgery

Purpose: To investigate the changes in Tenon's capsule fibroblast (HTF) proliferation and their expressions of transforming growth factor-beta (TGF-beta) and matrix metalloproteinases (MMPs) in patients with long-term use of topical antiglaucoma medications, and to evaluate the potential effect of these medications on the outcome of glaucoma filtering surgery for primary open-angle glaucoma (POAG). Methods: HTFs isolated from the conjunctiva of ten POAG patients and ten control patients with cataract or retinal detachment were tested for their in vitro proliferation capacity. RT-PCR (reverse-transcription polymerase chain reaction) was performed to detect the expressions of TGF-beta and MMP mRNAs in the HTFs, and the expression of TGF-beta 2 protein was detected immunohistochemically. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of TGF-beta 1 in the supernatant of the HTFs treated with the topical antiglaucoma agents. Results: The HTFs from the POAG patients showed significantly higher proliferative activity than those from the control patients (P = 0.0013). The HTFs in the POAG group showed significantly higher expressions of TGF-beta 2 and TGF-beta 3 mRNA and lower MMP-9 mRNA than the control HTFs. MMP-3 mRNA was not detected in the HTFs in POAG groups, but lowly expressed in the control HTFs. The HTFs in the POAG group had a significantly higher expression of TGF-beta 2 protein; TGF-beta 1 protein was not detected in the control HTFs, but was highly expressed in the POAG group. Treatment of the HTFs with latanoprost resulted in a 4-fold increase in TGF-beta 1 expression in both groups, which was comparable for the expression after the exposure. Conclusions: Long-term use of some topical antiglaucoma medications might be associated with enhanced HTF proliferation and abnormal expressions of TGF-beta and MMPs, which might have promoted scarring of the filtering blebs following glaucoma filtering surgery.