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N. H. Victor Chong, Robert A. Alexander, Trevor Gin, Alan C. Bird, Philip J. Luthert; TIMP-3, Collagen, and Elastin Immunohistochemistry and Histopathology of Sorsby’s Fundus Dystrophy. Invest. Ophthalmol. Vis. Sci. 2000;41(3):898-902.
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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.
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