Active transforming growth factor-β2 in the aqueous humor of posterior polymorphous corneal dystrophy patients

Abstract

Purpose: Posterior polymorphous corneal dystrophy (PPCD) is characterized by abnormal proliferation of corneal endothelial cells. It was shown that TGF-β2 present in aqueous humor (AH) could help maintaining the corneal endothelium in a G1-phase-arrest state. We wanted to determine whether the levels of this protein are changed in AH of PPCD patients.

Methods: We determined the concentrations of active TGF-β2 in the AH of 29 PPCD patients (42 samples) and 40 cadaver controls (44 samples) by ELISA. For data analysis the PPCD patients were divided based on either the molecular genetic cause of their disease as PPCD1 (37 samples), PPCD3 (1 sample) and PPCDx (not linked to a known PPCD loci, 4 samples) or on the presence (17 samples) or absence (25 samples) of secondary glaucoma or on whether they had undergone penetrating keratoplasty (PK, 32 samples) or repeated PK (rePK, 7 samples).

Results: The level of active TGF-β2 in the AH of all PPCD patients (mean ± SD; 386.98 ± 114.88 pg/ml) in comparison to the control group (260.95 ± 112.43 pg/ml) was significantly higher (P = 0.0001). Compared to the control group, a significantly higher level of active TGF-β2 was found in the PPCD1 (P = 0.0005) and PPCDx (P = 0.0022) groups. Among patients the levels of active TGF-β2 were not significantly affected by gender, age, secondary glaucoma or by the progression of dystrophy when one or repeated PK were performed.

Conclusion: The levels of active TGF-β2 in the AH of PPCD patients are significantly higher than control values, and thus the increased levels of TGF-β2 could be a consequence of the PPCD phenotype and can be considered as another feature characterizing this disease.

Fig 1. Active transforming growth factor (TGF)-β2 levels in the AH measured by ELISA.

(A) Distribution of the active TGF-β2 levels in the AH of controls and all posterior polymorphous corneal dystrophy patients (PPCD_all), and (B) of controls and the groups of patients with different molecular genetic causes: PPCD1, PPCD3, and PPCDx. Multiple data points from the same patient were averaged and the average value presented as one data point. Active TGF-β2 levels are presented as data distribution and box plots enhanced with mean ± SD. Displayed P-values reflect statistical significance of observed differences in the mean values of TGF-β2 obtained as fixed effects in otherwise unadjusted linear mixed-effects model.