Ocular cicatricial pemphigoid (OCP) is a systemic,
autoimmune disease characterised by conjunctival
scarring that is often progressive. The pathophysiology of the
fibrosis is unknown. This study aimed to determine which fibrogenic
cytokines are present in the conjunctiva in patients with acute and chronic OCP as a first stage in determining the mechanisms of
fibrosis. Conjunctival biopsies from patients with acute, subacute and chronic OCP (n=13) were compared to normal conjunctiva (n=10). Production of
mRNA for, and expression of, transforming growth-beta1, 2 and 3 (
TGF-beta),
TGF-beta receptor,
platelet derived growth factor (PDGF) and
fibroblast growth factor (FGF) were assessed using in situ hybridisation and immunohistochemistry.
Acute disease showed increased levels of
mRNA for
TGF-beta1 and 3, mainly in stromal fibroblasts and macrophages. In the stroma, there were concordant increases in latent and activated
TGF-beta1 and 3 and
TGF-beta receptor expression by fibroblasts. There were no significant increases in the expression of
TGF-beta2, PDGF or FGF in
acute disease. No
cytokines or receptors were significantly increased in
chronic disease. Acutely inflamed conjunctiva in OCP is associated with significant stromal levels of
TGF-beta1 and 3 but not PDGF or FGF and none were increased in
chronic disease. This suggests that
TGF-beta may have a key role in the pathogenesis of the
fibrosis. The absence of fibrogenic
cytokines in chronic progressive OCP provides support for the proposal that fibroblasts in OCP conjunctiva may remain functionally and morphologically abnormal after the withdrawal of
cytokine influences.