Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy

ABSTRACT: Neurotrophic Keratopathy (NK),classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK. Our data emphasized a proteome modulation duringrhNGF treatment related to an increase in DNA synthesis, an activation ofboth BDNF signaland IL6 receptor.Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+)correlated with the EVs carrying IL6R (CD126+) togetherassociated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Neurotrophic Keratoconjunctivitis

SUBMITTER: Maria Concetta Cufaro  

LAB HEAD: Piero Del Boccio

PROVIDER: PXD025408 | Pride | 2022-02-14

REPOSITORIES: Pride