Biomed Res Int. 2015;2015:846501.

MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes.


Fulzele S1, El-Sherbini A2, Ahmad S3, Sangani R1, Matragoon S4, El-Remessy A4, Radhakrishnan R2, Liou GI2.
  • 1Department of Orthopedics, Georgia Regents University, Augusta, GA, USA.
  • 2Department of Ophthalmology, Georgia Regents University, Augusta, GA 30912, USA.
  • 3Rabigh College of Science and Arts, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 4Program in Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA.



Hyperglycemia- (HG-) Amadori-glycated albumin- (AGA-) induced activation of microglia and monocytes and their adherence to retinal vascular endothelial cells contribute to retinal inflammation leading to diabetic retinopathy (DR). There is a great need for early detection of DR before demonstrable tissue damages become irreversible. Extracellular adenosine, required for endogenous anti-inflammation, is regulated by the interplay of equilibrative nucleoside transporter with adenosine deaminase (ADA) and adenosine kinase. ADA, including ADA1 and ADA2, exists in all organisms. However, because ADA2 gene has not been identified in mouse genome, how diabetes alters adenosine-dependent anti-inflammation remains unclear. Studies of pig retinal microglia and human macrophages revealed a causal role of ADA2 in inflammation. Database search suggested miR-146b-3p recognition sites in the 3′-UTR of ADA2 mRNA. Coexpression of miR-146b-3p, but not miR-146-5p or nontargeting miRNA, with 3′-UTR of the ADA2 gene was necessary to suppress a linked reporter gene. In the vitreous of diabetic patients, decreased miR-146b-3p is associated with increased ADA2 activity. Ectopic expression of miR-146b-3p suppressed ADA2 expression, activity, and TNF-α release in the AGA-treated human macrophages. These results suggest a regulatory role of miR-146b-3p in diabetes related retinal inflammation by suppressing ADA2.

PMID: 25815338


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List of Abbreviations:

DR, diabetic retinopathy

ARs, adenosine receptors

ENT, equilibrative nucleoside transporter

ADA1, adenosine deaminase-1

ADGF, adenosine deaminase growth factor

AK, adenosine kinase

5’NT, 5’nucleotidase

Ecto 5’NT, ecto 5’nucleotidases, or CD3, CD29

miR, micro RNA

HG, hyperglycemia






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