Expression Pattern of Tenascin-C, Matrilin-2, and Aggrecan in Diseases Affecting the Corneal Endothelium

Abstract

Purpose: The aim of this study was to examine the expression pattern of tenascin-C, matrilin-2, and aggrecan in irreversible corneal endothelial pathology such as pseudophakic bullous keratopathy (PBK) and Fuchs’ endothelial corneal dystrophy (FECD), which most frequently require corneal transplantation. Materials and methods: Histological specimens of corneal buttons removed during keratoplasty were investigated in PBK (n = 20) and FECD (n = 9) and compared to healthy control corneas (n = 10). The sections were studied by chromogenic immunohistochemistry (CHR-IHC) and submitted for evaluation by two investigators. Semiquantitative scoring (0 to 3+) was applied according to standardized methods at high magnification (400x). Each layer of the cornea was investigated; in addition, the stroma was subdivided into anterior, middle, and posterior parts for more precise analysis. In case of non-parametric distribution Mann–Whitney test was applied to compare two groups. Kruskal–Wallis and Dunn’s multiple comparisons tests have been applied for comparison of the chromogenic IHC signal intensity among corneal layers within the control and patient groups. Differences of p < 0.05 were considered as significant. Results: Significantly elevated tenascin-C immunopositivity was present in the epithelium and every layer of the stroma in both pathologic conditions as compared to normal controls. In addition, also significantly stronger matrilin-2 positivity was detected in the epithelium; however, weaker reaction was present in the endothelium in PBK cases. Minimal, but significantly elevated immunopositivity could be observed in the anterior and posterior stroma in the FECD group. Additionally, minimally, but significantly higher aggrecan immunoreaction was present in the anterior stroma in PBK and in the posterior stroma in both endothelial disorders. All three antibodies disclosed the strongest reaction in the posterior stroma either in PBK or in FECD cases. Conclusions: These extracellular matrix molecules disclosed up to moderate immunopositivity in the corneal layers in varying extents. Through their networking, bridging, and adhesive abilities these proteins are involved in corneal regeneration and tissue reorganization in endothelial dysfunction.

Corneal keratocytes, fibroblasts, and myofibroblasts exhibit distinct transcriptional profilesin vitro

“…Alterations in ECM composition during wound healing elicits changes in cellular behavior through interactions with cell membrane receptors. Tenascin C (TNC) and fibronectin (FN1), which in this study were highly expressed in fibroblasts and myofibroblasts, respectively, have been investigated extensively due to their roles in inflammation, wound healing, and tissue remodeling 86,101,102 . Tenascin C modulates cellular adhesion and migration through several integrin receptors (α8β1, α9β1, α7β1), which also showed enhanced gene expression in fibroblasts.…”

“…Changes in ECM composition within the corneal stroma likely also elicit changes in cell behavior via interactions with integrin-containing receptors. Tenascin C (TNC) and fibronectin (FN1), which have been investigated extensively for their involvement in inflammation, wound healing, and tissue remodeling 97, 112, 113 , were found to be highly expressed in corneal fibroblasts and myofibroblasts, respectively. Tenascin C modulates cell adhesion and migration via several integrin receptors, including α8β1 and αvβ1, the subunits of which exhibited elevated gene expression among our cultured fibroblasts.…”