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miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature

Elizabeth Curtiss1, Li Liu1, Jena J Steinle1

  • 1Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USA.

Experimental Eye Research
|July 8, 2018
PubMed

Insights

MicroRNA 15a (miR15a) reduces inflammatory proteins and Foxo1 in the retinal vasculature. Loss of miR15a increases NLRP3 inflammasome signaling, suggesting miR15a is key to diabetic retinal pathology.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Immunology

Background:

  • Diabetic retinopathy involves inflammatory cytokines.
  • MicroRNA 15a (miR15a) has shown potential in reducing inflammation.
  • The role of miR15a in the NLRP3 inflammasome pathway in diabetic retinal pathology is unclear.

Purpose of the Study:

  • To investigate the effect of miR15a on NLR pyrin domain 3 (NLRP3) proteins in the retinal vasculature.
  • To determine if miR15a directly binds to forkhead box protein O1 (Foxo1).

Main Methods:

  • Analyzed protein levels of Foxo1, NLRP3, cleaved caspase 1, and IL-1β in miR15a overexpressing and knockout mice retinas.
  • Utilized primary human retinal endothelial cells (REC) cultured in high glucose and transfected with miR15a mimic.
  • Verified miR15a expression via quantitative PCR and assessed direct binding to Foxo1 using a luciferase assay.

Main Results:

  • Loss of miR15a in mice increased levels of Foxo1, IL-1β, NLRP3, and cleaved caspase 1.
  • In high glucose conditions, miR15a mimic transfection in REC decreased Foxo1 and NLRP3 levels.
  • miR15a was confirmed to directly bind to Foxo1.

Conclusions:

  • miR15a directly binds Foxo1 and regulates NLRP3 inflammasome activation in retinal vasculature.
  • miR15a plays a protective role by reducing inflammasome proteins and Foxo1 levels, suggesting therapeutic potential in diabetic retinopathy.
Keywords:
FOXO1aNLRP3 inflammasome proteinsRetinal endothelial cellsmiR15a

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