NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP)

Objective In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkA 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. Materials and Methods Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkA NGFR /p75 NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkA NGFR /p75 NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. Results OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. A dvanced OCP-FBs showed higher αSMA expression associated with higher p75 NTR and lower trkA NGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75 NTR . NGF exposure did not affect trkA NGFR levels in early OCP-FBs while decreased both αSMA/p75 NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. Conclusions Taken together, these data are suggestive for a NGF/p75 NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75 NTR might be viewed as a potential therapeutic target.