TGF beta receptor II (Tbr2) deficiency in keratocytes results in corneal ectasia.

PURPOSE: We hypothesized that TGF beta receptor 2 (Tbr2) deletion (Δ) in the corneal stroma (Tbr2Δ/Δcst ) can result in corneal thinning and generate a potential model for cornea ectasia.

METHODS: Corneal thickness of Tbr2Δ/Δcst and Tbr2Δ/+cst was examined with Optical Coherence Tomography (OCT) at post-natal (P) days 42 and 70, respectively. Histological H&E staining, transmission electron micrograph (TEM), and immunofluorescence staining (IFS) were harnessed to examine corneal cell morphology, proliferation, differentiation, and collagen fibrils.

RESULTS: Slit-Lamp revealed that corneas were transparent in both Tbr2Δ/Δcst and Tbr2Δ/+cst , however, Tbr2Δ/Δcst cornea was 33.5% and 42.9% thinner as compared with those of Tbr2Δ/+cst at P42 and P70, respectively. H&E and semithin section staining with toluidine blue-O confirmed that Tbr2Δ/Δcst cornea has a thinner stroma. In contrast, the epithelium in Tbr2Δ/Δcst was substantially thicker in Tbr2Δ/Δcst . The cell proliferation marker Ki67 expression level increased ∼9% in Tbr2Δ/Δcst corneal epithelium as compared with that in Tbr2Δ/+cst , however, the Krt14 and Krt12 expression pattern was not obviously changed in Tbr2Δ/Δcst corneal epithelium. It was noticed that Col1a1 expression was substantially reduced in Tbr2Δ/Δcst as compared with that in Tbr2Δ/+cst . TEM showed that keratocytes were unhealthy and stromal collagen fibril density was significantly reduced in Tbr2Δ/Δcst as compared with that in Tbr2Δ/+cst cornea. Moreover, mechanical eye-rubbing on Tbr2Δ/Δcst resulted in corneal hydrops and edema.

CONCLUSION: Tbr2 in keratocytes is indispensable for the corneal stroma at postnatal homeostasis. The cornea phenotype manifested in these Tbr2Δ/Δcst mice resemble corneal ectasia disease in humans.