Temporal and Spatial Expression of Transforming Growth Factor B (TGF B) in Ocular Tissue After Experimental Glaucoma Filtration Surgery

Abstract

Abstract: : Purpose: The healing response after glaucoma filtration surgery (GFS) is the major obstacle to long–term intraocular pressure control and arrest of glaucomatous progression. TGFß is well recognized as a potent mediator of conjunctival scarring. This study was designed to identify the changes in ocular TGFß expression associated with GFS. Methods: A time course study was performed in which 16 New Zealand white rabbits underwent modified GFS. Anterior segment tissues were sampled from 4 animals per group on days 1, 3, 8 and 14 after surgery. Real–time TaqMan PCR and ELISA techniques determined TGFß2, TGFß1, Collagen I, III, α smooth muscle actin mRNA and protein expression. Results: In unoperated eyes relative TGFß2 mRNA expression was highest in the ciliary body (CB) (Rank order: CB >> iris > cornea > conjunctiva > sclera). GFS significantly upregulated TGFß2 mRNA expression in the CB (day 3; P<0.001 and day 14; P<0.05), iris (day 3; P<0.01) and cornea (day 14; P<0.05); and TGFß1 conjunctival mRNA expression (day 3, P<0.05). Control aqueous TGFß2 concentration was 2.4 ng/mL (total) and 1.6 ng/mL (active). GFS significantly reduced active TGFß2 levels in the aqueous at all time points. Bleb tissue total TGFß2 protein content on day 3 (84.0 pg/ml) was 16–fold that of control tissue (5.60 pg/mg). Conclusions: Aqueous from unoperated eyes contains high levels of TGF ß2 protein. After GFS conjunctival tissue has elevated TGFß1 and ß2 expression. Conjunctival exposure to high levels of TGFß2 from the aqueous and local tissues is likely to stimulate conjunctival scarring and drainage bleb failure.

Keywords: wound healing • growth factors/growth factor receptors