Keratoconus associated with corneal stromal amyloid deposition containing TGFBIp.
Keratoconus associated with corneal stromal amyloid deposition containing TGFBIp.
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DOI：
10.1097/ico.0b013e31818c9003
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发表时间：
2009-06
期刊：
影响因子：
2.8
通讯作者：
Aldave AJ
中科院分区：
文献类型：
--
作者：
Tai TY;Damani MR;Vo R;Rayner SA;Glasgow BJ;Hofbauer JD;Casey R;Aldave AJ
报告圆锥角膜患者间质淀粉样沉积物的鉴定和特征。对两名临床诊断为圆锥角膜的患者的切除的角膜纽扣进行了Masson三色、刚果红、阿尔新蓝和高碘酸-希夫染色的组织化学分析以及TGFBI蛋白产物（TGF β）、前白蛋白、溶菌酶、κ和λ轻链表达的免疫组织化学分析。在从两名患者收集DNA后，扩增TGFBI的外显子4和11-14并测序，以搜索先前与营养不良性角膜基质淀粉样蛋白沉积相关的突变。角膜按钮的光学显微镜检查显示基质变薄，上皮基底膜异常和Bowman层的局灶性破坏。鉴定出多个基质沉积物，其用Masson三色染色成红色，用高碘酸-希夫染色成粉红色，用刚果红染色成红色;刚果红染色的沉积物用交叉偏振透镜显示出双折射和二色性。免疫组织化学染色显示间质沉积物与TGF β 1 β抗体反应，但与前白蛋白、溶菌酶或κ和λ轻链抗体无反应。TGFBI外显子4，11-14的筛选揭示了两个先前鉴定的SNP在两个个体中以杂合状态存在，但没有其他编码区变体。本文报告两例圆锥角膜合并继发性淀粉样蛋白沉积的病例。虽然在基质沉积物中鉴定了TGF β 1 β，但在任一受影响个体中均未鉴定出先前报道的TGF β 1 β淀粉样蛋白突变，表明先前未描述的基质淀粉样蛋白沉积机制。
To report the identification and characterization of stromal amyloid deposits in patients with keratoconus. The excised corneal buttons from two patients diagnosed clinically with keratoconus underwent histochemical analysis with Masson trichrome, Congo red, Alcian blue and periodic acid-Schiff stains as well as immunohistochemical analysis for the TGFBI protein product (TGFBIp), prealbumin, lysozyme, kappa and lambda light chain expression. Following the collection of DNA from both patients, exons 4 and 11–14 of TGFBI were amplified and sequenced to search for mutations previously associated with dystrophic corneal stromal amyloid deposition. Light microscopic examination of the corneal buttons revealed stromal thinning, epithelial basement membrane abnormalities and focal disruption of Bowman’s layer. Multiple stromal deposits were identified that stained red with Masson trichrome, pink with periodic acid-Schiff, and red with Congo red; the Congo red-stained deposits demonstrated birefringence and dichroism with crossed polarized lenses. 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. Screening of TGFBI exons 4, 11–14 revealed two previously identified SNPs present in the heterozygous state in both individuals, but no other coding region variants. Two cases of keratoconus with clinically unsuspected, presumed secondary stromal amyloid deposition are described. Although TGFBIp is identified in the stromal deposits, no previously reported amyloidogenic mutations are identified in TGFBI in either affected individual, indicating a previously undescribed mechanism of stromal amyloid deposition.