title: NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).
abstract: 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.
  
  
  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 trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR 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. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA 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 αSMA/p75NTR expression and TGFβ1/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.
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micera
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stampachiacchiere
authors.affiliation: Department of Ophthalmology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Zazzo
authors.affiliation: Department of Ophthalmology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sgrulletta
authors.affiliation: IRCCS-G.B. Bietti Foundation, Rome, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cortes
authors.affiliation: Glaucoma & Retinal Degeneration Research Group, Visual Neurosciences, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, United Kingdom.|The Western Eye Hospital, Imperial College Healthcare Trust, Marylebone Road, London, NW1 5QH, United Kingdom.
authors.forename: Eduardo Maria
authors.initials: EM
authors.lastname: Normando
authors.affiliation: Ophthalmology, Dept. Organi di senso, University of Rome "Sapienza", Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lambiase
authors.affiliation: Department of Ophthalmology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonini
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010390:Pemphigoid, Benign Mucous Membrane / Q000378:metabolism*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D020932:Nerve Growth Factor; D020917:Receptor, trkA