Abstract
Purpose :
Progression of diabetic retinopathy continues even when hyperglycemic insult is reversed by normal glycemia, suggesting a ‘metabolic memory’ phenomenon, however, the molecular mechanism of this metabolic memory phenomenon is still elusive. Diabetes alters expression of many LncRNAs (RNA with more than 200 nucleotides and no open reading frame for translation), and these LncRNAs can regulate gene expression by remodeling chromatin or through sequence complementarity with RNAs or DNA. The aim of study was to identify aberrantly expressed LncRNAs in the retina that fail to reverse when hyperglycemia is terminated.
Methods :
Streptozotocin-induced diabetic rats were kept in either continuous poor glycemic control for 8 months (PC group, blood glucose>400mg/dl) or in poor glycemic control for 4 months, followed by in good control (blood glucose<150mg/dl) for 4 additional months (Rev group). Retinal RNA was isolated by RNeasy Kit, and microarray analysis was performed by Arraystar. Differentially expressed LncRNAs and mRNAs were identified through Volcano filtering, and among those 10 LncRNAs each, upregulated and downregulated, were confirmed by qRT-PCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the common altered biological processes and pathways among the groups.
Results :
Over10,300 LncRNAs were identified in the retina from normal rats, and among those 1479 LncRNAs had differential expression in the PC group (769 up- and 710 down-regulated) and 491 in the Rev group (372 up-and 139 down-regulated). GO analysis indicated 203 up- and 165 down- regulated common biological processes between PC and Rev groups, and KEGG analysis showed 22 common pathways, mainly implicated in cell-cell signaling, polyol pathway and cell death.
Conclusions :
Identification of aberrantly expressed LncRNAs with similar patterns in PC and Rev groups could serve as the potential molecular markers for the metabolic memory associated with the continued progression of diabetic retinopathy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.