| Year | 2004 | Journal | Int J Exp Pathol |
| Volume | 85 | Issue | 4 |
| Pages | A45-77 | PubMed ID | 15312129 |
| Mgi Jnum | J:104714 | Mgi Id | MGI:3612664 |
| Doi | 10.1111/j.0959-9673.2004.0390a.x | Citation | Cooper LJ, et al. (2004) British Society for Matrix Biology meeting. Manchester, 5-6 april 2004. Abstracts. (An ultrastructural investigation of dermatopontin-knockout mouse corneas). Int J Exp Pathol 85(4):A45-77 (A59) |
| abstractText | Full text of Abstract: British Society for Matrix Biology Meeting. A59. An ultrastructural investigation of dermato-pontin-knockout mouse corneas. L.J. Cooper,* A.J. Bentley,* I.A. Nieduszynski,* N.J. Fullwood,* T.S. Ellis,* A. Thomson,* A. Utanil,+ H. Sinkai+ and G.M. Brown*. *Department of Biological Sciences, Lancaster University, Lancaster, UK; +Department of Dermatology, Chiba University School of Medicine, Chuouku, Chiba, Japan. Introduction. the corneal stroma is composed of a network of heterotypic collagen fibrils, proteoglycans and matrix proteins. Transparency of the tissue principally requires the uniformity of fibril diameters and interfibrillar distances and the presence of a quasi-hexagonal lattice arrangement of parallel fibrils. Keratan sulfate proteoglycans (KSPGs) have a crucial role and the KS chains are clearly required for the maintenance of transparency. Undersulfation of corneal KS results in tissue opacity and the lumican (a KSPG) knockout mouse shows corneal opacity and the disruption of collagen fibril diameters and interfibrillar distances (Chakravarti et al. 1998). Biochemical analysis has shown that dermatopontin is an abundant component of the extracellular matrix and that it interacts with KSPGs via the KS chains. This study aims to determine whether dermatopontin has a direct role in corneal matrix organization by investigating the corneal ultrastructure of dermatopontin-null (dpt-/-) mouse corneas. Materials and methods. Conventional light microscopy was used to compare the corneal thickness of dpt-/- mice (Takeda et al. 2002) with that of the wild-type. Collagen fibril distribution was studied using transmission electron microscopy and the datasets analysed using SIS-pro image analysis software to determine fibrillar volume, shape factor, fibril diameter and spacing. Results. Light microscopy demonstrated that dpt-/- corneas show a 24% reduction in average stromal thickness compared to wild-type (P <0.001). The epithelium and Descemet's membrane appear normal. Examination of dpt-/- stroma by transmission electron microscopy indicates a significant disruption to lamellar organization in the posterior region while the central and anterior regions appear largely unaffected compared to wild-type. The collagen fibrils in dpt-/- stroma show a pronounced increase in interfibrillar spacing as well as exhibiting a lower fibril volume fraction. There is no apparent difference in fibril diameter between dpt-/- and wild-type mice. Discussion. Collectively, these data suggest that dermatopontin plays a key role in collagen fibril organization and deposition. Like the cornea from lumican-knockout mice (Chakravarti et al. 1998), the defects in collagen organization in dpt-/- cornea appear to be most severe in the posterior stroma. It is likely that dermatopontin interacts with the KS chains on lumican and this interaction is involved in the maintenance of stromal architecture. References. Chakravarti S. et al. (1998) Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J. Cell Biol. 141, 1277-1286. Takeda U. et al. (2002) Targeted disruption of dermatopontin causes abnormal collagen fibrillogenesis. J. Invest. Dermatol. 119, 678-683. |
