title: miR-146a is upregulated during retinal pigment epithelium (RPE)/choroid aging in mice and repressesIL-6andVEGF-Aexpression in RPE cells.
abstract: OBJECTIVE
  MicroRNA-146a (miR-146a) has been proposed as a marker for age-associated inflammation, or "inflammaging", acting as a negative regulator of cellular senescence and pro-inflammatory signaling pathways. However, the regulation and function of miR-146 during ocular aging remains unclear. Here we propose that miR-146 is regulated during aging of the retina and choroid, and functions in retinal pigment epithelial (RPE) cells to regulate key genes involved in inflammation and angiogenesis.
  
  
  METHODS
  The expression of miR-146a and miR-146b was examined in the neuroretina and RPE/choroid in mice aged from 2 months to 24 months. Then, the effect of synthetic miR-146a mimetic onIL-6andVEGF-Aexpression was analyzed in RPE cells treated with and without TNF-α.
  
  
  RESULTS
  miR-146a and miR-146b was upregulated during aging of RPE/choroid but not neuroretina, supporting tissue-specific regulation of aging-related miRNAs in retinal tissues. Overexpression of miR-146a by miRNA mimics inhibitedVEGF-Aand TNF-α-inducedIL-6expression.
  
  
  CONCLUSIONS
  Elevation of miR-146a and miR-146b in the aging RPE/choroid but not neuroretina suggests a role for miRNAs in inflammaging in the RPE/choroid. miR-146a overexpression inhibits the expressionIL-6andVEGF-Ain the RPE cells, supporting a negative feedback regulation mechanism by which inflammatory pathways may be dysregulated in RPE during aging.
authors.affiliation: Fushun Ophthalmology Hospital, Fushun, Liaoning Province, 113006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA.
authors.forename: Qinbo
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA; Department of Ophthalmology, Tulane University, New Orleans, LA, 70118, USA.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Wang