NGF Modulates trkA.sup.NGFR/p75.sup.NTR in [alpha]SMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP)

In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkA.sup.NGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for [alpha]SMA, NGF and trkA.sup.NGFR /p75.sup.NTR expression. Subcultures were exposed to NGF and evaluated for [alpha]SMA, NGF, trkA.sup.NGFR /p75.sup.NTR expression as well as TGF[beta]1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. OCP-conjunctivas showed [alpha]SMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher [alpha]SMA expression associated with higher p75.sup.NTR and lower trkA.sup.NGFR expression, as compared to early counterparts. [alpha]SMA expression was in keeping with disease severity and correlated to p75.sup.NTR . NGF exposure did not affect trkA.sup.NGFR levels in early OCP-FBs while decreased both [alpha]SMA/p75.sup.NTR expression and TGF[beta]1/IL4 release. These effects were not observed in advanced OCP-FBs. Taken together, these data are suggestive for a NGF/p75.sup.NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75.sup.NTR might be viewed as a potential therapeutic target.