Abstract
Abstract: :
Purpose: To determine the localization of Growth differentiation factor 5 (GDF–5) and bone morphogenic protein (BMP–7) in the human eye under normal and pathologic conditions. Intraocular bone/cartilage is seen in a wide spectrum of ocular disorders. However, the pathogenesis of bone/cartilage formation in the eye is unclear. GDF–5 and BMP–7 are important multifunctional cytokines that play critical roles in bone and cartilage formation. In this study we used immunohistochemistry to investigate the presence and possible roles of these cytokines in the human eye. Material and Methods:Sections from human eyes included fetal eyes (n=5), normal adult eyes (n=4), eyes with osseous metaplasia (n=8), and teratoid medulloepithelioma and fetal eyes with intraocular cartilage (n=3). Immunohistochemistry was performed using indirect immunofluorescence with anti GDF–5 and anti BMP–7 antibodies. The staining intensity was evaluated semiquantitatively. Results: GDF–5: Moderate intensity of GDF–5 immunoreactivity (IR) was noted in keratocytes of adult normal eyes and along Muller cell processes of fetal eyes. There was minimal or no anti GDF–5 IR of other tissues. In contrast, intense IR was seen in the RPE, especially adjacent to areas of osseous metaplasia, in the osteoblasts and in zones of RPE fibrous metaplasia. Intense IR was noted in the ciliary epithelium in zones of chondroid formation and also in the ciliary epithelium in eyes with osseous metaplasia not in proximity to osseous areas. BMP–7: Mild to moderate anti–BMP–7 IR was seen in adult and fetal cornea and ciliary epithelium. Like GDF–5, increased anti BMP IR was seen in the RPE surrounding and within osseous tissue, zones of RPE fibrous metaplasia. Additionally in eyes with intraocular bone and cartilage, keratocytes, the ciliary epithelium, and retina had increased IR when compared to normal eyes. GDF–5 and BMP–7 appeared to co–localize in the RPE and ciliary epithelium of eyes with bone and cartilage. Conclusion:The marked increase of GDF–5 and BMP–7 in the RPE and ciliary epithelium in eyes with bone and cartilage suggests that these proteins play an important role in bone and cartilage metaplasia.
Keywords: immunohistochemistry • growth factors/growth factor receptors