NGF Modulates trkANGFR/p75NTR in [alpha] SMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP): e0142737

Objective In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR 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 [alpha] SMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for [alpha] SMA, NGF, trkANGFR/p75NTR expression as well as TGF[Beta]1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. Results OCP-conjunctivas showed [alpha] SMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher [alpha] SMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. [alpha] SMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both [alpha] SMA/p75NTR expression and TGF[Beta]1/IL4 release. These effects were not observed in advanced OCP-FBs. Conclusions Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target.