6533b831fe1ef96bd1299918

RESEARCH PRODUCT

Synthetic Polyclonal-Derived CDR Peptides as an Innovative Strategy in Glaucoma Therapy

Caroline ManicamNatarajan PerumalNorbert PfeifferKatharina BellFranz H. GrusCarsten SchmelterKristian Nzogang Fomo

subject

<i>Sus scrofa domestica</i>lcsh:MedicineRetinal ganglionEpitopeArticleSus scrofa domestica03 medical and health scienceschemistry.chemical_compound0302 clinical medicineImmune systemMedicine030304 developmental biology0303 health sciencesHTRA2synthetic CDR peptidesbusiness.industrylcsh:RautoimmunityRetinalGeneral MedicineProtein ubiquitinationCell biologyglaucomachemistryneuroprotectionSignal transductionbusinessVDAC2030217 neurology & neurosurgeryEx vivo

description

The pathogenesis of glaucoma is strongly associated with the occurrence of autoimmune-mediated loss of retinal ganglion cells (RGCs) and additionally, recent evidence shows that specific antibody-derived signature peptides are significantly differentially expressed in sera of primary-open angle glaucoma patients (POAG) compared to healthy controls. Synthetically antibody-derived peptides can modulate various effector functions of the immune system and act as antimicrobial or antiviral molecules. In an ex vivo adolescent glaucoma model, this study, for the first time, demonstrates that polyclonal-derived complementarity-determining regions (CDRs) can significantly increase the survival rate of RGCs (p = 0.013). We subsequently performed affinity capture experiments that verified the mitochondrial serine protease HTRA2 (gene name: HTRA2) as a high-affinity retinal epitope target of CDR1 sequence motif ASGYTFTNYGLSWVR. Quantitative proteomic analysis of the CDR-treated retinal explants revealed increased expression of various anti-apoptotic and anti-oxidative proteins (e.g., VDAC2 and TXN) compared to untreated controls (p &lt

yearjournalcountryeditionlanguage
2019-08-01Journal of Clinical Medicine
10.3390/jcm8081222http://europepmc.org/articles/PMC6723090