Age-related distribution and potential role of SNCB in topographically different retinal areas of the common marmoset Callithrix jacchus, including the macula

Exp Eye Res. 2019 Aug;185:107676. doi: 10.1016/j.exer.2019.05.016. Epub 2019 May 23.

Abstract

Evidence of an age-related increase of β-synuclein (SNCB) in several parts of the visual system including the retina has been reported. SNCB is thought to function as an antagonist of α-synuclein in neurodegenerative diseases, but the exact role of SNCB remains unclear. The presented work studies two different aspects of the onset and role of SNCB in the retinal pigment epithelium (RPE). First, the topographical and intracellular distributions of SNCB in the RPE of non-human marmoset monkey (Callithrix jacchus) were evaluated in paraffin-embedded eyes and RPE whole mounts from different developmental stages (neonatal, adolescent, and adult). Thus, revealed distinct lifetime-related alterations of the topographical and intracellular distributions of SNCB in the primate macula compared to the retinal periphery. Furthermore, the function and influences of SNCB on ARPE-19 cells and primary porcine RPE (ppRPE) cells were characterized by exposing these cells with recombinant SNCB (rSNCB) at different concentrations. Moreover, apoptosis, protein- and mRNA-expression levels of factors of the p53/MDM2 signaling cascade and inflammation- and oxidation-related genes were investigated. The observed dose-depended decreased apoptosis rates together with the PLD2 mediated activation of the p53 pathway promotes senescence-related processes in SNCB exposed common ARPE-19 cells from human origin. Further, increased HMOX1 and NOX4 levels indicate increased oxidative stress and inflammatory responses triggered by SNCB. The obtained differences in the distribution of SNCB in primate RPE together with alterations of cellular functions in rSNCB-exposed RPE cells (e.g., ARPE-19, ppRPE) support SNCB-related effects like inflammatory response and stress-related properties on RPE over lifetime. The possible functional relevance of SNCB in physiological aging converting into a pathophysiological condition should be investigated in further studies.

Keywords: Age-related macular degeneration; Aging; Beta-synuclein; Callithrix jacchus; RPE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Apoptosis
  • Callithrix
  • Cell Line
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / physiology
  • Heme Oxygenase (Decyclizing) / metabolism
  • Humans
  • Male
  • NADPH Oxidase 4 / metabolism
  • Oxidative Stress
  • Paraffin Embedding
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology
  • Signal Transduction
  • Sus scrofa
  • Tumor Suppressor Protein p53 / genetics
  • beta-Synuclein / metabolism*
  • beta-Synuclein / pharmacology

Substances

  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • beta-Synuclein
  • Heme Oxygenase (Decyclizing)
  • NADPH Oxidase 4
  • Proto-Oncogene Proteins c-mdm2