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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

TIMP-3, collagen, and elastin immunohistochemistry and histopathology of Sorsby's fundus dystrophy.

PURPOSE: Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP-3) gene have previously been identified in patients with Sorsby's fundus dystrophy (SFD). We evaluated the ocular distribution of TIMP-3 and other extracellular constituents in SFD. METHODS: The eyes of an SFD donor with a confirmed TIMP-3 mutation were examined using histologic techniques demonstrating connective tissue, calcium, and lipid. Immunohistochemical analyses were performed using antibodies against TIMP-3, collagen type IV, V, and VI, laminin, fibronectin, elastin, and fibrillin. Electron microscopy also was used. RESULTS: A subretinal pigment epithelium (sub-RPE) deposit similar to that previously described was seen. A morphologically similar but different deposit was present internal to the nonpigmented ciliary epithelium (NPCE). Both deposits contained collagens, elastin, glycosaminoglycans, lipids, and calcium. Immunolabeling of TIMP-3 was found in the basement membrane of the NPCE, Bruch's membrane, and choroidal vessels in normal control subjects. In SFD, immunolabeling of TIMP-3 also was present in the sub-RPE deposit and in the inner portion of the ciliary body deposit. TIMP-3 immunoreactivity was more extensive in the SFD eye. The pattern of elastin immunoreactivity was remarkably similar to that of TIMP-3. Electron microscopy revealed a morphologically altered elastic layer of the Bruch's membrane. CONCLUSIONS: Sub-RPE TIMP-3 immunoreactivity appears more extensive in SFD than in control subjects. There is also a correspondence between TIMP-3 and elastin immunoreactivies, which invites speculation as to a link between the SFD TIMP-3 mutation and altered elastin processing. The accumulation of abnormal material in SFD is more widespread than previously reported. In view of this, SFD might be better termed Sorsby's ocular epitheliopathy.[1]


  1. TIMP-3, collagen, and elastin immunohistochemistry and histopathology of Sorsby's fundus dystrophy. Chong, N.H., Alexander, R.A., Gin, T., Bird, A.C., Luthert, P.J. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
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