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T. Tai, M. R. Damani, R. Vo, A. J. Aldave, B. J. Glasgow; Keratoconus Associated With Corneal Stromal Amyloid Deposition Containing TGFBIp. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4314.
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The composition of secondary amyloid deposition in keratoconus is not known. Here we report TGFBIp (the protein product of TGFBI) expression in amyloid deposits of keratoconus patients in the absence of mutations in TGFBI.
Histochemical studies included stains for Masson trichrome, Congo red, and periodic acid-Schiff in paraffin embedded sections of excised corneal buttons from two patients. Immunohistochemistry was performed for TGFBIp, prealbumin, lysozyme, kappa and lambda light chain expression. DNA was collected from both patients for PCR amplification and direct sequencing of TGFBI exons 4, 11, 12, 13 and 14, in which all mutations associated with dystrophic corneal stromal amyloid deposition have been identified to date.
Light microscopic examination of the excised corneal buttons revealed multiple stromal deposits that stained red with Masson trichrome, pink with periodic acid-Schiff, and red with Congo red. The Congo red deposits show green birefringence and dichroism with crossed polars. Immunohistochemical staining demonstrated reactivity of the stromal deposits with antibodies to TGFBIp, but no reactivity with antibodies against prealbumin, lysozyme, or kappa and lambda light chains. Accompanying histologic findings include stromal thinning, epithelial basement membrane duplication with irregular thinning and focal disruptions of Bowman’s layer. Screening of TGFBI exons 4, 11, 12, 13 and 14 revealed two previously identified SNPs present in the heterozygous state in both individuals, (p.Leu472Leu; rs1133170 and p.Phe540Phe; rs4669), but no other coding region variants.
Keratoconus may be rarely associated with clinically unsuspected stromal amyloid. Secondary amyloid deposits in keratoconus contain TGFBIp rather than other proteins usually associated with secondary amyloidosis, in the absence of TGFBI mutations. The mechanism of TGFBIp deposition in keratoconus appears to be different from that of the TGFBI dystrophies.
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