Background.Ultrastructural studies of idiopatic epiretinal (iERM) membranes in the past have proven inadequate for identifying the origin of the involved cells due to their ability to undergo morphological changes via transdifferentiation. Thus, molecular techniques can represent an innovative and indispensable area of interest to make more clarity on iERMs¿ pathogenesis. Much of our understanding related to the interdependence of cytokines and growth factors involved in iERM formation is incomplete and there is no Literature on molecular characterization of the two different types of iERMs so far identified. Purpose.The present project aims to evaluate the role of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) together with their precursors and receptors in the pathogenesis of the two different types of iERMs and their correlations with clinical parameters.Design.Prospective, cross-sectional study.Methods. Patients diagnosed with vitreoretinal interface disorders suitable for surgical treatment will be subjected to a complete preoperative ophthalmological evaluation. Partecipants will undergo standard three port pars plana Vitrectomy with MER+Internal Limiting (MLI) Membrane removal and specific analytical tests will be performed to evaluateNGF, proNGF,trkA,trkB,p75,BDNF andproBDNF in iERMs samples. All patients will be visited at 1,3,6 and 12 months after surgery. Transmission Electronic microscopy will be performed in order to ultrastructurally differentiate the two types of iERMs. Results.Levels of Neurotrophines (NTs), precursors and receptors will be evaluated in surgically excised iERMs. Partecipants will be followed for one year studying the correlations between NGF profiles observed in iERMs¿ samples and clinical and instrumental parameters registered preoperatively and at 1,3,6 and finally 12 months after surgery. The association between biomarkers¿ expression and the two distinct clinicopathological types of iERMs will be studied
The expression of NTs and their receptors can represent a valid contribution in clarifying the pathogenesis of the two distinct clinicopathological types of idiopatic epiretinal membranes, recently described in Literature. The complete preoperative clinical and instrumental ophthalmological evaluation and the subsequent evaluations at 1, 3, 6 and 12 months after surgery, offer the opportunity to compare visual acuity at baseline and visual outcome after surgery and to correlate such results with the type of epiretinal membrane after ultrastructural analysis. The same comparison can be performed between pre and post-operative SD-OCT imaging, pre and post- visual acuity and the type of membrane. Only a few recent studies analized the role of NTs¿ pathway in iERMs, involving mainly NGF and TGF-ß. This is the first study in Literature that aims to describe the role of such a wide panel of NTs, precursors and receptors in iERMs: NGF, proNGF, BDNF, proBDNF, p75 (NTR), trkA (NGFR) and trkB (NGFR). Moreover this is the first study in which there is a comparison between analytic results, visual acuity (at different times pre and after surgery), SD-OCT features and type of iERM defined ultrastructurally. Our results are expected to have a major impact on basic research, clinical and surgical knowledge, and pharmaceutical industry. The results of the present project will advance knowledge on clinical and surgical science in ocular physiopathology and disease treatment. Specifically, the study will define the involvement of NTs pathway in patients with iERM, a challenging and potentially blinding disease