Bone morphogenetic proteins (BMPs) and
activins are multifunctional
growth factors, which also affect wound healing and tissue
fibrosis. To determine their putative role in conjunctival wound healing and
scarring, we investigated the expression of various BMPs,
BMP receptors, and
activins in normal and scarred human conjunctival tissue and in cultured human Tenon's capsule fibroblasts on the
mRNA and
protein level.
Messenger RNA expression of BMP-2, BMP-3, BMP-4,
BMP-5,
BMP-6,
BMP-7, the
BMP receptors type I (BMPR-IA, BMPR-IB) and II (BMPR-II), and of
activin A and B was investigated by semi-quantitative RT-PCR in normal conjunctival specimens and in scarred filtering
blebs as well as in cultured Tenon's capsule fibroblasts obtained from patients with
primary open-angle glaucoma (POAG), pseudoexfoliation (PEX)
glaucoma and
cataract. Immunohistochemistry was used to study the
protein expression of BMP-2, BMP-4,
BMP-6,
BMP-7, and
activin A in normal and scarred conjunctival tissue as well as in cultured Tenon's capsule fibroblasts. BMP-2, BMP-3, BMP-4,
BMP-6,
BMP-7, all
BMP receptors, and
activin A were expressed on the
mRNA and
protein level in conjunctival biopsies without showing any differences between groups of patients. The
mRNA and
protein expression of both
BMP-6 and
activin A was found to be significantly increased in
scar tissue compared with normal conjunctiva and could be immunolocalized to epithelial cells, vascular endothelia, stromal fibroblasts, and macrophage-like cells. However, no significant increase in receptor gene expression was observed in
scar tissue. With the exception of
BMP-7, all
growth factors and receptors were also expressed in cultured Tenon's fibroblasts without showing any differences between cultures derived from normal and scarred conjunctival specimens. These findings suggest various BMPs and
activin A as components of the conjunctival
cytokine meshwork regulating tissue homeostasis and wound healing and provide evidence that alterations in the expression of
BMP-6 and
activin A, in particular, are associated with conjunctival
scarring. Modulation of BMP/
activin activities may, therefore, be explored as new approaches for managing postoperative conjunctival
scarring responses in
glaucoma patients.