Abstract
PurposePosterior 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.MethodsWe 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).ResultsThe 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.ConclusionThe 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.
Highlights
Posterior polymorphous corneal dystrophy (PPCD) is a bilateral disorder affecting all layers of the cornea but most severely its posterior part, i.e., the endothelium, Descemet’s membrane and the deepest stromal layers [1, 2]
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
The levels of active TGF-β2 in the aqueous humor (AH) of PPCD patients are significantly higher than control values, and the increased levels of TGF-β2 could be a consequence of the PPCD phenotype and can be considered as another feature characterizing this disease
Summary
Posterior polymorphous corneal dystrophy (PPCD) is a bilateral disorder affecting all layers of the cornea but most severely its posterior part, i.e., the endothelium, Descemet’s membrane and the deepest stromal layers [1, 2]. PPCD is genetically heterogeneous: PPCD1 (OMIM #122000) is caused by mutations in the OVOL2 promoter [3], PPCD2 (OMIM #609140) has been associated with mutations in COL8A2 [4] and PPCD3 (OMIM #609141) with mutations in ZEB1 genes [5]. PPCD affects at least 1:100,000 inhabitants in the Czech Republic and most patients carry a disease-causing founder mutation in OVOL2 [3]. In one family linkage exclusion to the PPCD1 locus and a lack of mutations in the coding sequence of ZEB1 and COL8A2 suggest the possibility of the existence of a novel disease locus [10, 11]. The human corneal endothelium is a monolayer of flat hexagonal cells, which are normally arrested in the G1-phase of the cell cycle but retain their proliferative capacity [12] that may be renewed in vivo and in vitro by the disruption of cell-cell contacts and by the addition of growth factors into the anterior chamber or culture medium [13,14,15]
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