Research Mentor Name

Ahmed Ibrahim

Research Mentor Email Address

gt5379@wayne.edu

Institution / Department

Ophthalmology, Visual and Anatomical Sciences. Wayne State University School of Medicine

Document Type

Research Abstract

Research Type

basicbio

Level of Research

no

Abstract

Introduction: A major cause of blindness is proliferative diabetic retinopathy (PDR), and there is limited data on the nucleic acid (NA) profiles in PDR. We characterized the profiles of NAs in human retinal endothelial cells (HRECs) subjected to high glucose (HG) and hypoxia (Hyp) - common risk factors associated with PDR.

Methods: HRECs were treated with osmotic control (Mannitol, 25 mM) or high glucose (HG, 25 mM) for 5 days, followed by normoxia or hypoxia (Hyp, 2% O2) for 24 hours. Pathway enrichment analysis from the significant metabolites in the Hyp+HG vs control comparison was subsequently performed.

Results: The precursors ribose-5-phpshate and inosine monophosphate were elevated in the HG+Hyp condition. The purines adenosine and the combined concentration of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) exhibited a similar pattern. The ratio of adenosine triphosphate to AMP + ADP was decreased in the same inter-groups contrast. The same exact pattern for the combination mono and diphosphate as well as the ratio of the triphosphate to mono and diphosphate was observed for the nucleotides guanosine, uridine and cytidine. Pathway analysis revealed 18 significant pathways, including phosphate bond hydrolysis by NTPDase proteins and interconversion of nucleotide di-and triphosphates.

Conclusion: We show that nucleotide mono and diphosphates are selectively elevated when compared to their triphosphate analogues in HRECs in an experimental model of PDR. These findings suggest that in a stressful environment of high glucose and low oxygen, both vitreous and endothelial cells may not favor the utilization of energy rich nucleotide triphosphates.

Disciplines

Medicine and Health Sciences

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