Toyran S, Lin A Y, Edward D P
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1905 W Taylor Street, L217, Chicago, IL 60612, USA.
Br J Ophthalmol. 2005 Jul;89(7):885-90. doi: 10.1136/bjo.2004.056374.
BACKGROUND/AIMS: Intraocular bone is seen in a wide spectrum of ocular disorders. The pathogenetic mechanisms of bone formation in the eye are unclear. Growth differentiation factor-5 (GDF-5), bone morphogenic protein-7 (BMP-7), and transforming growth factor beta-1 (TGF beta1) are multifunctional cytokines that have important roles in bone formation. Immunohistochemistry was used to localise GDF-5, BMP-7, and TGF beta1 in the human eye to determine their role in intraocular bone formation.
Paraffin embedded sections from human eyes included fetal eyes (n = 5), normal adult eyes (n = 4), eyes with osseous metaplasia (n = 8), and eyes with focal fibrous metaplasia of the retinal pigment epithelium (RPE) without osseous metaplasia (n = 2). Immunohistochemistry was performed using indirect immunofluorescence with antibodies to GDF-5, BMP-7, and TGF beta1. The staining intensity was evaluated semiquantitatively in the RPE, retina, ciliary epithelium, and cornea; and analysed statistically.
When compared with normal adult eyes, which showed no RPE immunoreactivity, the RPE metaplasia surrounding areas of osseous metaplasia showed mild GDF-5 and moderate BMP-7 (p = 0.004) intracytoplasmic immunoreactivity. In contrast, trace GDF-5 and mild BMP-7 staining was seen in zones of RPE fibrous metaplasia in areas not associated with osseous metaplasia. Mild intracytoplasmic TGF beta1 expression was seen in the RPE metaplasia surrounding the bone when compared with adult eyes. Both fetal and adult eyes showed trace to mild GDF-5 and BMP-7 labelling of the non-pigmented ciliary epithelium which was increased in the eyes with osseous metaplasia. In eyes with osseous metaplasia, a significant decrease in GDF-5 and BMP-7 labelling was noted in fetal keratocytes (p = 0.0159 for both antibodies) when compared to adult eyes. Also, a significant decrease in BMP-7 labelling was seen in keratocytes in eyes with osseous metaplasia (p = 0.0162).
The increase in GDF-5, BMP-7, and TGF beta1 immunoreactivity in zones of RPE metaplasia in eyes with osseous metaplasia suggests that these proteins have an important role in intraocular ectopic bone formation.
背景/目的：眼内骨可见于多种眼部疾病。眼内骨形成的发病机制尚不清楚。生长分化因子-5（GDF-5）、骨形态发生蛋白-7（BMP-7）和转化生长因子β1（TGFβ1）是在骨形成中起重要作用的多功能细胞因子。采用免疫组织化学方法对人眼内的GDF-5、BMP-7和TGFβ1进行定位，以确定它们在眼内骨形成中的作用。
人眼石蜡包埋切片包括胎儿眼（n = 5）、正常成人眼（n = 4）、骨化生眼（n = 8）和无骨化生的视网膜色素上皮（RPE）局灶性纤维化生眼（n = 2）。使用针对GDF-5、BMP-7和TGFβ1的抗体通过间接免疫荧光进行免疫组织化学检测。对RPE、视网膜、睫状体上皮和角膜的染色强度进行半定量评估，并进行统计学分析。
与无RPE免疫反应性的正常成人眼相比，骨化生周围区域的RPE化生显示出轻度的GDF-5胞浆内免疫反应性和中度的BMP-7胞浆内免疫反应性（p = 0.004）。相比之下，在与骨化生无关区域的RPE纤维化生区域可见微量的GDF-5和轻度的BMP-7染色。与成人眼相比，骨周围的RPE化生区域可见轻度的TGFβ1胞浆内表达。胎儿眼和成人眼的无色素睫状体上皮均可见微量至轻度的GDF-5和BMP-7标记，在骨化生眼中其标记增加。与成人眼相比，骨化生眼中胎儿角膜细胞的GDF-5和BMP-7标记显著减少（两种抗体的p值均为0.0159）。此外，骨化生眼中角膜细胞的BMP-7标记也显著减少（p = 0.0162）。
骨化生眼中RPE化生区域GDF-5、BMP-7和TGFβ1免疫反应性的增加表明这些蛋白质在眼内异位骨形成中起重要作用。
